Reduced Incidence of Long Coronavirus Disease Referrals to the Cambridge University Teaching Hospital Long Coronavirus Disease Clinic

Abstract

Long coronavirus disease (COVID [LC]) constitutes a potential health emergency as millions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections lead to chronic symptoms. We must understand whether vaccines reduce LC because this has major implications for health policy. We report a 79% reduction in LC referrals correlating with vaccination in the United Kingdom.

Long COVID (also known as post-acute sequalae of SARS-CoV-2 infection) poses a serious health burden for society. There is no consensus of the exact symptoms, duration, or prevalence of LC. It is, however, evident that some patients experience debilitating multisystemic symptoms such as fatigue, myalgia, memory problems, and shortness of breath, just to mention a few, more than 6 months after acute COVID 2019 (COVID-19). Even more concerning is that there are a significant number of patients who have not fully recovered 2 years since the initial infection. This greatly diminishes LC sufferers’ quality of life, as well as exerting a heavy burden on the healthcare system, families of those affected, and having a negative impact on the economy [1].

Given the magnitude and impact of LC, it is vital that we understand whether vaccination reduces the incidence or severity of LC symptoms. Establishing whether vaccines reduce LC risk would provide key information in understanding the mechanistic underpinnings of LC. Additionally, if breakthrough infections are less likely to lead to LC, this affects decisions on policies such as masking to reduce SARS-CoV-2 spread, “zero COVID” as a long-term strategy and the use of further booster vaccinations. Indeed, as antibodies wane after booster vaccines, we would expect to see more breakthrough infections and potentially higher rates of LC cases. If that turns out to be the case, then yearly booster vaccines might be cost-effective for reducing morbidity from LC.

Two recent publications suggest that vaccination strongly reduced LC symptoms at 1–3 months after infection [2–4], but another study using a cohort of US Army veterans suggests a more modest effect size at 6 months (15% reduction) [5]. We believe that these differences are likely because of different data collection methods as well as the populations studied. It is conceivable that vaccination may reduce the severity of LC without full resolution of all symptoms. In this scenario, we would expect that vaccinated individuals would be less likely to seek medical treatment for LC but may still report LC symptoms if asked to complete a health questionnaire.

At the Cambridge University Teaching Hospital, the initial long COVID clinic was set up in May 2020. Patients are referred to the clinic based on a number of criteria, one of which is symptom duration of at least 5 months. These patients tend to be those on the severe end of the symptom spectrum, having been referred following assessment by a community multidisciplinary team that includes a general practitioner, mental health practitioners, physiologist, and occupational therapists, among other specialists.

We have noticed a 79% drop in the number of patients being referred to the clinic from August 2021 to June 2022, compared with August 2020 to July 2021 (Figure 1). This effect has so far been sustained until at least June 2022, despite 4 times more cases per month of acute COVID-19 in England across the same time periods [6]. This change is notable as the decrease begins in August 2021, 5 months after the British population started receiving second doses of COVID-19 vaccines in March 2021. Taken in context, this observation points toward vaccination in the UK playing a role in reducing the rates of the most severe LC cases.

Figure 1.

The number of patients referred to the Cambridge University Teaching Hospital Long COVID clinic has dropped since August 2021. Black circles: number of patients referred that month. Black crosses and dotted line: 6-month moving average.

Although changes in variant could explain differences in LC rates, we are not aware of any data that suggest a strong enough difference to explain our observations. Our observed reduction in LC rates in August 2021 were from patients experiencing symptoms for 5 months, which would suggest a change beginning in March 2021. This occurs too early for the Delta wave, which began in April 2021, but correlates well with the second doses of vaccination in the United Kingdom. Our recruitment criteria have not changed over this time, leading us to rule this out as a possible explanation. We cannot fully rule out prior infections providing immunity that protects against LC from reinfections; however, primary infections were more common than reinfections around March and April 2021 [7].

We also observe no changes in symptoms between those referred for LC before or after vaccination for any of the major symptoms such as fatigue (73% prevaccination, 76% postvaccination) and shortness of breath (18% prevaccination vs 23% postvaccination).

In summary, we have observed a significant reduction in the most severe cases of LC since the introduction of vaccines in the United Kingdom. Vaccination has not changed the symptoms of LC, but has likely reduced symptom severity. Our data point toward vaccination being an important tool to reduce the burden of LC for society. They also suggest that immunity before infection reduces LC risk, although the mechanisms behind this remain to be elucidated. One potential factor to consider is that vaccines reduce the severity of acute COVID-19 symptoms, leading to a reduction in post-COVID sequelae and subsequent reduction in LC severity.

It is not yet clear if immunity from a prior infection protects against LC, nor whether reinfections with SARS-CoV-2 hold the same risk of LC as a primary infection. Given the possibility that LC is caused by autoimmunity triggered by infection, or by persistent viral infections, it is plausible that each reinfection poses a cumulative risk of LC.

We also do not yet know what level of immunity is required to protect against LC. As immunity wanes over time, booster shots may be necessary to minimize LC risk, and variant specific booster shots may be more efficacious. These questions are paramount to our understanding, treating and preventing Long COVID.

Notes

Acknowledgments. The authors thank the staff and patients at CUH NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Financial support. This work was funded by the Addenbrooke’s Charitable Trust (900276 to N. S.) and an NIHR award (G112259 to N. S.) and supported by the NIHR Cambridge Biomedical Research Centre.

Ethics. The Long COVID study patients were recruited and consented under the Cambridge COVID-19 NIHR BioResource joint Consent Form (Research Ethics Committee NRES number [REC] T1gC1) study NBR87. Informed consent was obtained from all participants for the rest of the study.

Author notes

Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.