Differences in clinical presentation with long covid following community and hospital infection, and associations with all-cause mortality: English sentinel network database study (Preprint)
Authors: Meza-Torres Bernardo , Delanerolle Gayathri , Okusi Cecilia , Mayer Nikhil , Anand Sneha , McCartney Jack , Gatenby Piers , Glampson Ben , Chapman Martin , Curcin Vasa , Mayer Erik , Joy Mark , Greenhalgh Trisha , Delaney Brendan , de Lusignan Simon 
Published: March 2022

BACKGROUND

Long covid (LC) is defined as fatigue, breathlessness, cognitive dysfunction and a variety of other symptoms occurring after coronavirus-2019 disease (COVID-19). (1,2) Over a million people in the UK are estimated to have prolonged symptoms after COVID-19, with 60% of long covid patients reporting extended symptoms lasting months, and 240,000 people with symptoms limiting day-to-day activity. (3,4) The spectrum of symptoms imply widespread involvement of organs and there is a recognisable pattern of long covid disease resulting from autonomic dysfunction and mast cell disorder. (5) The Office for National Statistics (ONS) suggests that the prevalence of long covid is greater in females, middle-aged people, those from the most deprived areas, and those with an activity-limiting health condition or disability. (4) Symptoms are wide-ranging but fatigue, shortness of breath, and cognitive difficulties (termed ‘brain fog’ by patients) are most commonly reported. (6)

In late 2020 there was a release of International Classification of Disease (ICD) and Systematised Nomenclature of Medicine (SNOMED) clinical terms to support long covid coding (termed post-COVID condition) but recording in primary care electronic records varied. (7,8) Primary care data, however, remains the most useful source of epidemiological data outside hospital records and bespoke surveys to understand the symptoms that long covid patients present to primary care following documented COVID-19 infection. (6) There is a need to characterise the prevalence, risk factors and symptom patterns in long covid patients using routine clinical data to understand the symptoms people present with to primary care following COVID-19, and whether presentation and post-acute mortality differs in people who were not hospitalised.

This study reports the symptoms, sociodemographic profile, and outcomes of people identified as having long covid in English primary care. Our study has four components: (1) A comparison of clinical symptoms of people with long covid before and after COVID-19. (2) A description of the characteristics of people with long covid compared to those without long covid. (3) A comparison of those with long covid that were hospitalised with COVID-19 versus those that were not. (4) An analysis of all-cause mortality in people with long covid.

OBJECTIVE

This study was conducted as part of the Predicting Risk of Hospital Admission in Patients With Suspected COVID-19 in a Community Setting (RECAP) project. (9–11) RECAP included creating a phenotype for LC via an observational study. The population characteristics, baseline data, and our LC phenotype, were published in the study protocol. (12) The protocol also set out the details of the comparisons undertaken in this study. These were: (1) Undertaking a before and after comparison of the number of symptoms identified by ONS as more common in LC; (2) Comparing sociodemographic, comorbid and exposure characteristics of people coded by their GP with LC with people who were not; (3) Comparing characteristics of people with LC who had their index infection in hospital with those who had a community infection; (4) An analysis of all-cause mortality in people with LC. The study period included COVID-19 cases between 1st March 2020 and 1st April 2021, with a follow-up period of a further six months, up to latest 30th September 2021.

METHODS

We used routine data from the nationally representative Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7.4million), applying a pre-defined long covid phenotype and grouped by whether the index illness was in hospital or community. We conducted a before and after analysis of pre-specified long covid symptoms identified by the Office of National Statistics, comparing symptoms presented between one and six months after their index infection matched with the same months one year previously. We conducted logistic regression analysis, quoting odds ratios with 95% confidence intervals, reporting differences between those with an index community infection compared to those who had been hospitalised, and separately associations with all-cause mortality.

RESULTS

5.6% (n=428,588) and 1.8% (n=7,600) of patients respectively had a coded diagnosis of COVID-19 and diagnosis or referral for long covid. People coded as having long covid were significantly more likely to have presented to primary care after diagnosis than people without (odds ratios 2.66 [2.46-2.88] for those with index community infection and 2.42 [2.03-2.89] for those hospitalised). Following an index community infection, patients were more likely to present with non-specific symptoms (odds ratio 3.44 [3.00-3.95], p<0.001) than following a hospital admission (odds ratio 2.09 [1.56-2.80], p<0.001). Mental health sequelae were more commonly associated with hospital admission index infections (odds ratio 2.21 [1.64-2.96]) compared to community (odds ratio 1.36 [1.21-1.53], p<0.001).

People presenting to primary care following hospital infection were more likely to be male (odds ratio 1.43 [1.25-1.64], p<0.001), more socioeconomically deprived (odds ratio 1.42 [1.24-1.63], p<0.001); and to have multi-morbidity (odds ratio 1.41 [1.26-1.57], p<0.001) than those presenting after an index community infection.

All-cause mortality in people with long covid was associated with increasing age; male gender (odds ratio 3.32 [1.34-9.24], p<0.01) and higher multi-morbidity score (odds ratio 2.11 [1.34-3.29], p<0.001). One or more vaccine doses was associated with reduced odds of mortality (odds ratio 0.10 [0.03-0.35], p<0.001).

CONCLUSIONS

The low percentage (1.8%) of people recorded as having long covid following COVID-19 reflects either low prevalence or under-recording. The characteristics and comorbidities of those presenting with long covid following a community infection are different from those who were hospitalised with their index infection. This study provides insights into the presentation of long covid in primary care and implications for workload.