EDITORIALS
1 Institute of Applied Health Research,
University of Birmingham,
Birmingham, UK
2 University Hospitals Birmingham NHS
Foundation Trust, Birmingham, UK
Correspondence to: P Adab
p.adab@bham.ac.uk
Cite this as: BMJ 2022;377:o1431
http://dx.doi.org/10.1136/bmj.o1431
Published: 15 June 2022
the bmj | BMJ 2022;377:o1431 | doi: 10.1136/bmj.o1431
Comorbidities and covid-19
BMJ: first published as 10.1136/bmj.o1431 on 15 June 2022. Downloaded from http://www.bmj.com/ on 15 May 2023 by guest. Protected by copyright.
Better understanding is essential for health system planning
Peymané Adab, 1 Shamil Haroon, 1 Margaret E O’Hara, 2 Rachel E Jordan1
Over 530 million people worldwide are estimated to Long term effects
have had covid-19 by June 2022, resulting in more
Although most people with covid-19 recover fully,
than 6.3 million deaths.1 Although most people have
some have longer term symptoms (long
few symptoms or mild to moderate illness, a
covid)—usually persisting beyond 35 weeks.12 Both
substantial minority are at higher risk of more severe
the definition and estimated prevalence of long covid
disease (requiring hospital admission) and adverse
vary widely, but one recent international systematic
outcomes, including death and long covid. This is
review of studies reported that around 43% of adults
particularly true for people with comorbidities. Our
with covid-19 still have at least one symptom 28 days
understanding of which conditions increase risk, and
after infection, rising to 57% among those admitted
their relative importance to adverse outcomes is still
to hospital.13
evolving.
Symptoms of long covid are wide ranging but most
Initial case series, often unadjusted and with limited
commonly include fatigue, anosmia, dyspnoea,
generalisability, provided preliminary insights.2
cough, and myalgia.14 A UK analysis of primary care
Subsequently, increasing numbers of higher quality
records for 486 149 community patients with
observational studies have attempted to unpick these
confirmed covid-19 showed that reporting persistent
associations. The US Centers for Disease Control and
symptoms beyond 12 weeks was associated with many
Prevention regularly reviews all such studies to
pre-existing conditions, including chronic obstructive
update the list of conditions associated with greater
pulmonary disease, fibromyalgia, anxiety, and coeliac
risk of severe covid-19 and death.3 While risks
disease, in addition to risk factors such as obesity,
generally increase with age and are higher among
tobacco smoking, being female, and socioeconomic
men, strong evidence now shows increased risks for
deprivation.15
people with various health conditions, including
chronic kidney disease, diabetes, lung and liver Furthermore, evidence is growing that new chronic
diseases, cardiovascular disease, obesity, diseases can occur after acute covid-19. Data from a
immunodeficiency, certain disabilities, and mental US administrative claims database showed that 14%
health conditions. of adults who had had covid-19 developed new
clinical conditions within six months; a 1.65% higher
Risks are highest for people with complicated
incidence than that seen after other viral infections.16
diabetes, obesity, and anxiety related disorders
Clinical sequelae included interstitial lung disease,
(relative risk about 1.3 compared with people without
respiratory failure, congestive heart failure,
these conditions), and less for those with
arrythmia, and type 2 diabetes.16 The cluster of
cardiovascular disease (relative risk roughly 1.1).4
symptoms and clinical outcomes differed by age,
Evidence is more limited for other conditions such
between men and women, and between those who
as overweight, sickle cell disease, and substance use
were and were not admitted to hospital. Although
disorders and inconsistent for asthma, hypertension,
pre-existing conditions and hospital admission were
and viral hepatitis. Although the exact mechanisms
associated with higher risk overall, some outcomes,
by which pre-existing conditions influence disease
such as mental health diagnoses, were increased
susceptibility and severity are not known,
irrespective of age and comorbidities.16 A large UK
inflammatory and hormonal pathways are
based cohort study of people admitted to hospital
postulated,5 as well as social factors such as living
with covid-19 reported similar findings.17
in crowded or institutionalised settings.6
Risk of SARS-CoV-2 infection, severe disease, and
One in five people worldwide are estimated to be at
death have reduced in populations with high vaccine
higher risk of adverse covid-19 outcomes based on
uptake.18 Nevertheless, breakthrough infection still
the prevalence of chronic conditions.7 The risk also
occurs, and there is some evidence that older people
increases with age and with greater number of
(>65 years) and those with underlying conditions
underlying conditions. Compared with someone
remain at greatest risk, possibly because vaccine
younger than 40 years, the risk of death increases
effectiveness wanes more quickly in these groups.19 20
fourfold for people aged 50-64, and more than 10-fold
Vaccines also reduce the risk and duration of long
for those aged over 85.8 Similarly, compared with
covid symptoms, but the effect is smaller than the
people with no underlying conditions, the risk of
reduction in mortality and severe disease.21
death is 1.5 and 3.8 times higher for those with one
comorbidity and over 10 comorbidities, respectively.4 We now have a better understanding of the conditions
These findings have been used to develop multiple that increase risk of severe covid-19, but unanswered
risk score calculators9 -11 to aid clinical decisions. questions remain about their role in longer term
outcomes. A better quantification of the relation
between comorbidities and different outcomes and
1
 EDITORIALS

the populations at risk is essential for future health system planning.

21 UK Health Security Agency COVID-19 Evidence Team. The effectiveness of vaccination against
Such information will also support policy decisions, allowing long covid: a rapid evidence briefing. 2022. https://www.icpcovid.com/sites/default/files/2022-
consideration of the differential economic, social, and health effects 02/Ep%20241-9%20UK%20Health%20Security%20Agency%20The%20effective-

BMJ: first published as 10.1136/bmj.o1431 on 15 June 2022. Downloaded from http://www.bmj.com/ on 15 May 2023 by guest. Protected by copyright.
of protective interventions, including societal restriction. ness%20of%20vaccination%20against%20long%20COVID%20Feb%202022.pdf

Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial
companies. The authors declare the following other interests: REJ has given one-off advice to Boehringer
Ingelheim unrelated to this topic. PA has received research grants from Zhejiang Yongning
Pharmaceuticals unrelated to this topic. ME’OH is a founding trustee of Long Covid Support
(https://www.longcovid.org/).
This article is made freely available for personal use in accordance with BMJ's website terms and
conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may
download and print the article for any lawful, non-commercial purpose (including text and data mining)
provided that all copyright notices and trade marks are retained.

Provenance and peer review: Commissioned; not externally peer reviewed.

1 Johns Hopkins University of Medicine. Coronavirus Resource Centre. 3 Jun 2022. https://coron-
avirus.jhu.edu/map.html
2 Jordan RE, Adab P, Cheng KK. Covid-19: risk factors for severe disease and death. BMJ
2020;368:m1198. doi: 10.1136/bmj.m1198. pmid: 32217618
3 National Center for Immunization and Respiratory Diseases (NCIRD) DoVD. Science brief: evidence
used to update the list of underlying medical conditions associated with higher risk for severe
covid-19. 2022. https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/underlying-
evidence-table.html
4 Kompaniyets L, Pennington AF, Goodman AB, etal. Underlying medical conditions and severe
illness among 540,667 adults hospitalized with covid-19, March 2020-March 2021. Prev Chronic
Dis 2021;18:E66. doi: 10.5888/pcd18.210123. pmid: 34197283
5 Bigdelou B, Sepand MR, Najafikhoshnoo S, etal. Covid-19 and preexisting comorbidities: risks,
synergies, and clinical outcomes. Front Immunol 2022;13. doi: 10.3389/fimmu.2022.890517.
6 Liu L, Ni S-Y, Yan W, etal. Mental and neurological disorders and risk of COVID-19 susceptibility,
illness severity and mortality: a systematic review, meta-analysis and call for action.
EClinicalMedicine 2021;40:101111. doi: 10.1016/j.eclinm.2021.101111. pmid: 34514362
7 Clark A, Jit M, Warren-Gash C, etalCentre for the Mathematical Modelling of Infectious Diseases
COVID-19 working group. Global, regional, and national estimates of the population at increased
risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study. Lancet
Glob Health 2020;8:e1003-17. doi: 10.1016/S2214-109X(20)30264-3. pmid: 32553130
8 Pennington AF, Kompaniyets L, Summers AD, etal. Risk of clinical severity by age and
race/ethnicity among adults hospitalized for covid-19-United States, March-September 2020.
Open Forum Infect Dis 2020;8:a638. doi: 10.1093/ofid/ofaa638. pmid: 33553477
9 Nafilyan V, Humberstone B, Mehta N, etal. An external validation of the QCovid risk prediction
algorithm for risk of mortality from covid-19 in adults: a national validation cohort study in England.
Lancet Digit Health 2021;3:e425-33. doi: 10.1016/S2589-7500(21)00080-7. pmid: 34049834
10 How we built our covid-19 risk estimator. Economist 2021 Mar 11.
https://www.economist.com/graphic-detail/2021/03/11/how-we-built-our-covid-19-risk-estimator
11 Coggon D, Croft P, Cullinan P, Williams A. Assessment of workers’ personal vulnerability to
covid-19 using ‘covid-age’. Occup Med (Lond) 2020;70:461-4.
doi: 10.1093/occmed/kqaa150. pmid: 32761080
12 Davis HE, Assaf GS, McCorkell L, etal. Characterizing long COVID in an international cohort: 7
months of symptoms and their impact. EClinicalMedicine 2021;38:101019.
doi: 10.1016/j.eclinm.2021.101019. pmid: 34308300
13 Chen C, Haupert SR, Zimmermann L, etal. Global prevalence of post-coronavirus disease 2019
(covid-19) condition or long covid: a meta-analysis and systematic review. J Infect Dis 2022.
doi: 10.1093/infdis/jiac136. pmid: 35429399
14 Aiyegbusi OL, Hughes SE, Turner G, etalTLC Study Group. Symptoms, complications and
management of long COVID: a review. J R Soc Med 2021;114:428-42.
doi: 10.1177/01410768211032850. pmid: 34265229
15 Subramanian A, Nirantharakumar K, Hughes S, etal. Assessment of 115 symptoms for long covid
(post-covid-19 condition) and their risk factors in non-hospitalised individuals: a retrospective
matched cohort study in UK primary care: Research Square ,
2022doi: 10.21203/rs.3.rs-1343889/v1.
16 Daugherty SE, Guo Y, Heath K, etal. Risk of clinical sequelae after the acute phase of SARS-CoV-2
infection: retrospective cohort study. BMJ 2021;373:n1098.
doi: 10.1136/bmj.n1098. pmid: 34011492
17 Ayoubkhani D, Khunti K, Nafilyan V, etal. Post-covid syndrome in individuals admitted to hospital
with covid-19: retrospective cohort study. BMJ 2021;372:n693.
doi: 10.1136/bmj.n693. pmid: 33789877
18 Yek C, Warner S, Wiltz JL, etal. Risk factors for severe covid-19 outcomes among persons aged
≥18 years who completed a primary covid-19 vaccination series—465 health care facilities, United
States, December 2020-October 2021. MMWR Morb Mortal Wkly Rep 2022;71:19-25.
doi: 10.15585/mmwr.mm7101a4. pmid: 34990440
19 Ranzani OT, Hitchings MDT, Dorion M, etal. Effectiveness of the CoronaVac vaccine in older
adults during a gamma variant associated epidemic of covid-19 in Brazil: test negative case-control
study. BMJ 2021;374:n2015. doi: 10.1136/bmj.n2015. pmid: 34417194
20 Menni C, May A, Polidori L, etal. COVID-19 vaccine waning and effectiveness and side-effects of
boosters: a prospective community study from the ZOE COVID Study. Lancet Infect Dis
2022;S1473-3099(22)00146-3. doi: 10.1016/S1473-3099(22)00146-3. pmid: 35405090

2 the bmj | BMJ 2022;377:o1431 | doi: 10.1136/bmj.o1431