Associations between SARS-CoV-2 infection and incidence of new chronic condition diagnoses: a systematic review

Figures & data

Figure 1. PRISMA flow diagram for a systematic review of the associations between SARS-CoV-2 infection and incidence of new chronic condition diagnoses. Template From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting.

Table 1. Study characteristics of included studies for a systematic review of new diagnoses of chronic conditions after SARS-CoV-2 infection.

Study Country Data source	Index time for SARS-CoV-2 infections	Study design N	Mean/ median follow-up, range If not reported, maximum range of FU?	Care type/setting for SARS-CoV-2 infected cases	Age range (years) % Female	% Hospitalized % in ICU	Comparator timing Test status of comparator group	Outcomes
Abel 2021 [32] United Kingdom Clinical Practice Research Datalink Aurum	Feb 2020 to Dec 2020	Retrospective cohort N = 11,923,105	Median (IQR) – 6.3 (4.0–9.3) weeks	Outpatient	16–80+ 50%	NA	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Mental disorders (anxiety disorders, depression, psychosis)
Ayoubkhani 2021 [33] United Kingdom Hospital Episode Statistics Admitted Patient Care and General Practice Extraction Service Data for Pandemic Planning and Research	Jan 2020 to Aug 2020	Retrospective cohort N = 95,560	Cov: Mean (SD) – 140 (50) days Con: Mean (SD) – 153 (33) days	Inpatient	0–70 + 45%	100 NR	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Cardiovascular disease (composite of arrhythmia, heart failure, myocardial infarction, and stroke); Chronic kidney disease (dialysis and kidney transplant); Diabetes (type 1 & type 2); Respiratory disorders
Bohlken 2022 [34] Germany IQVIA Disease Analyzer database	Mar 2020 to Sept 2021	Retrospective cohort N = 134,092	Cov: Mean – 158 days Con: Mean – 165 days	Outpatient	18–70+ 53.3%	NA	Concurrent >90% had test negative	Neurological conditions (mild cognitive disorder)
Chevinsky 2021 [35] United States Premier Healthcare Database Special COVID-19 Release	Mar 2020 to Jun 2020	Prospective cohort N = 148,892	Range 1–4 mos	Mixed	<18 (adult data not stratified by age)	11.4 NR	Concurrent No confirmed/ suspected SARS-CoV-2 infection	31 different conditions across 7 categories, but only reports “Children with COVID-19 were not more likely to experience new diagnoses than children without COVID-19,” with no effect size or variance reported and was thus unable to be included in the meta-analysis. Attempt to contact authors to obtain the data was not successful.
Cohen 2022 [36] United States UnitedHealth Database	Jan 2020 to Dec 2020	Retrospective cohort N = 226,380	Median (IQR) – 78 (30–175) days	Mixed	65+ 58%	27 6.4	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Cardiovascular disease (acute coronary disease, cardiogenic shock, cardiac arrhythmia, cardiomyopathy, congestive heart failure, coronary disease, hypertension, myocardial infarction, tachycardia); Chronic kidney disease; Diabetes (type 2); Mental disorders (mental health diagnosis, psychosis); Neurological conditions (dementia, encephalopathy, Guillain-Barre syndrome, migraine, peripheral neuropathy, seizure); Respiratory disorders (chronic respiratory failure, interstitial lung disease); Stroke
Daugherty 2021 [37] United States UnitedHealth Database	Jan 2019 to Oct 2020	Retrospective cohort N = 488,552	Median (IQR) – 87 (45-124) days	Mixed	18–65 52.5%	8.2 1.1	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Cardiovascular disease (acute coronary disease, arrythmia, cardiogenic shock, cardiomyopathy, congestive heart failure, coronary disease, hypertension, myocardial infarction, tachycardia); Chronic kidney disease; Diabetes (type 2); Mental disorders (mental health diagnosis, psychosis); Neurological conditions (Alzheimer’s disease, dementia, encephalopathy, Guillain-Barre syndrome, migraine, peripheral neuropathy, seizure); Respiratory disorders (chronic respiratory failure, interstitial lung disease); Stroke
Donnachie 2022 [38] Germany Bavarian COVID-19 Cohort	Jan 2020 to Jun 2021	Retrospective cohort N = 454,649	NR Followed up for 2 years	Outpatient	0–60+ 54%	NA	Concurrent >90% had test negative	Mental disorders (anxiety disorders, mood disorders); Neurological conditions (mild cognitive impairment)
Jacob 2022 [39] Germany IQVIA Disease Analyzer database	Mar 2020 to May 2021	Retrospective cohort N = 112,700	NR Maximum of 14 mos	Outpatient	18–70+ 52.3%	NA	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Mental disorders (anxiety disorders, depression)
Kompaniyets 2022 [40] United States HealthVerity	Mar 2020 to Jan 2022	Retrospective cohort N = 3,125,676	NR Minimum of 60 days to maximum of 365 days	Mixed	2to 17 50%	NR	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Cardiovascular disease (cardiac dysrhythmias); Chronic kidney disease; Diabetes; Mental disorders (anxiety disorders, mood disorder); Musculoskeletal disorders; Neurological conditions (nervous system disorder); Respiratory disorders (asthma); Stroke
Park 2021 [41] Korea National Health Insurance Service Database	Jan 2020 to Dec 2020	Retrospective cohort N = 260,883	NR Minimum of 0 days to maximum of 12 mos	Mixed	20–60+ 54.3%	NR	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Mental disorders (mental illness)
Pietropaolo 2022 [42] United States TriNetX COVID-19 Research Network	Jan 2020 to Jun 2021	Retrospective cohort N = 4,070,133	NR Minimum of 1 d to maximum of 18 mos	Mixed	0–30 45%	NR	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Diabetes (type 1 & type 2)
Qureshi 2022 [43] United States Cerner Real-World Data	Until July 2021	Retrospective cohort N = 20,806	Median (IQR) – 182 (113–277) days	Inpatient	0–70+ 39%	100 NR	Concurrent >90% had test negative	Neurological conditions (dementia)
Rao 2022 [44] US Electronic health record data from PEDSnet institutions	Mar 2020 to Oct 2021	Retrospective cohort N = 659,286	Cov: Mean (SD) – 4.6 (0.7) Weeks Con: Mean (SD) – 4.7 (0.7) weeks	Mixed	0–21 47.2%	6 2.2	Concurrent >90% had test negative	Mental disorders (mental health treatment); Neurological conditions (communication/motor disorders)
Rezel-Potts 2022 [45] United Kingdom Clinical Practice Research Datalink Aurum	Feb 2021 to Jan 2022	Retrospective cohort N = 857,300	Median – 12 mos	Mixed	— 56%	NR	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Cardiovascular disease (atrial arrhythmias, heart failure, myocardial infarction and ischaemic heart disease); Diabetes (type 1 & type 2); Stroke
Roessler 2022 [46] Germany Data from 6 German statuatory health insurance organizations: AOK Bayern – Die Gesundheitskasse, AOK PLUS, BARMER, BKKen, DAK Gesundheit, and Techniker Krankenkasse	By Jun 2020	Retrospective cohort N = 314,268	Cov: Mean (SD) – 236 (44) days Con: Mean (SD) – 254 (36) days	Mixed	0–18 48.1%	1 0.4	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Cardiovascular disease (cardiac arrhythmias, heart failure, heart murmurs, myocardial infarction, other cardiac arrhythmias); Mental disorders (adjustment disorder, anxiety disorders, depressive disorders, emotional and behavioural disorders, obsessive-compulsive disorder); Neurological conditions (chronic fatigue syndrome, developmental delay, dyslexia, facial nerve paralysis, headache, movement disorders, other coordination disorders/ataxia, seizures, speech and language disorders); Stroke
Tartof 2022 [16] United States Vaccine Safety Datalink	Mar 2019 to Mar 2021	Retrospective cohort N = 255,718	NR Maximum of 6 mos	Inpatient	0–85+ 53.7%	100 NR	Concurrent >90% had test negative	Diabetes; Mental disorder (anxiety disorders, psychosis); Stroke Only <18y data eligible for meta-analysis
Taquet 2022 [47] United States TriNetX COVID-19 Research Network	Jan 2020 to Mar 2022	Retrospective cohort N = 2,568,874	Cov: Mean (SD) – 213 (204) days Con: Mean (SD) – 223 (203) days	Mixed	0–65+ 57.8%	NR	Concurrent >90% had test negative	Mental disorders (anxiety disorders, mood disorders, psychotic disorder); Neurological conditions (cognitive deficit, dementia, Guillain-Barre syndrome, myoneural junction/muscle disease, nerve/nerve root/plexus disorder, Parkinsonism, seizure); Stroke
Taquet 2021 [48] United States TriNetX COVID-19 Research Network	Jan 2020 to Apr 2022	Retrospective cohort N = 89,558	NR 14 days to 90 days	Mixed	65+	NR	Concurrent >90% had test negative	Neurological conditions (dementia; other outcomes not analysed by age strata)
Wang 2022a [49] United States TriNetX COVID-19 Research Network	Feb 2020 to May 2021	Retrospective cohort N = 820,956	NR Maximum of 360 days	Mixed	65–85+ 57%	NR	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Neurological conditions (Alzheimer’s disease)
Wang 2022b [50] United States TriNetX COVID-19 Research Network	Jan 2019 to Mar 2022	Retrospective cohort N = 1,381,784	NR Minimum of 30 days to maximum of 12 mos	Mixed	20–65+ 54%	NR	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Cardiovascular disease (acute coronary disease, angina, atrial fibrillation and flutter, bradycardia, cardiac arrest, cardiogenic shock, cardiomyopathy, heart failure, ischaemic cardiomyopathy, myocardial infarction, tachycardia, ventricular arrhythmias); Stroke
Westman 2022 [51] Sweden SmiNET, Swedish National Patient Register	Feb 2020 to Dec 2021	Prospective cohort N = 2,445,113	NR Maximum of 22 mos	Mixed	21–100+ 51%	NR	Historical NA	Neurological conditions (epilepsy)
Xie 2022a [52] United States Department of Veterans Health Administration	Mar 2020 to Sept 2021	Prospective cohort N = 4,299,721	Cov: Median (IQR) – 352 (244–406) days Con: Median (IQR) – 352 (245–406) days	Mixed	0–65+ 11.5%	8.3 2.2	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Diabetes
Xie 2022b [53] United States Department of Veterans Health Administration	Mar 2020 to Jan 2021	Prospective cohort N = 5,827,407	Cov: Median (IQR) – 347 (317–440) days Con: Median (IQR) – 348 (318–441) days	Mixed	0–65+ 10%	10.9 3.5	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Cardiovascular disease (dysrhythmia, ischaemic heart disease); Stroke
Xu 2022 [54] United States Department of Veterans Health Administration	Mar 2020 to Jan 2021	Prospective cohort N = 5,815,067	Cov: Median (IQR) – 408 (378–500) days Con: Median (IQR) – 348 (318–441) days	Mixed	0–65+ 10%	10.8 3.4	Concurrent No confirmed/ suspected SARS-CoV-2 infection	Mental disorders (anxiety disorders, major depressive disorders, psychotic disorders, stress/adjustment disorders); Neurological conditions (Alzheimer's disease, memory problems)
Zarifkar 2022 [55] Denmark Electronic health records from Capital Region and Region Zealand	Feb 2020 to Nov 2021	Prospective cohort N = 238,699	NR Maximum of 12 mos	Mixed	18–80+ Inpatients: 51% female Outpatients:40% females	18.5 NR	Concurrent >90% had test negative	Neurological conditions (Alzheimer’s disease, Guillain-Barre syndrome, multiple sclerosis, myasthenia gravis, Parkinson's disease); Stroke

Con: control group; Cov: SARS-CoV-2 infected group; FU: follow-up; ICU: intensive care unit; IQR: interquartile range; mos: months; NA: not applicable; NR: not reported; SD: standard deviation.

Table 2. Risk of bias assessment according to JBI’s Cohort Studies tool.

Study	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9	Q10	Q11	Overall
Abel 2021	Y	N	U	Y	Y	Y	Y	U	U	U	Y	Moderate
Ayoubkhani 2021	N	N	Y	Y	Y	Y	Y	Y	Y	NA	Y	High
Bohlken 2022	Y	N	N	Y	Y	Y	Y	Y	Y	NA	Y	High
Chevinsky 2021	U	U	Y	Y	Y	Y	Y	N	U	U	U	Moderate
Cohen 2022	Y	N	Y	Y	Y	Y	Y	Y	Y	NA	Y	Moderate
Daugherty 2021	Y	N	Y	Y	Y	Y	Y	Y	Y	Y	Y	Moderate
Donnachie 2022	Y	Y	Y	Y	Y	Y	Y	Y	N	Y	N	High
Jacob 2022	Y	N	Y	Y	U	Y	Y	U	U	Y	U	Moderate
Kompaniyets 2022	Y	N	Y	Y	U	Y	Y	Y	U	Y	Y	Moderate
Park 2021	Y	N	U	Y	Y	Y	Y	Y	Y	NA	Y	Moderate
Pietropaolo 2022	Y	N	Y	Y	Y	Y	U	Y	U	U	Y	Moderate
Qureshi 2022	Y	Y	Y	Y	Y	Y	Y	Y	U	U	U	Moderate
Rao 2022	Y	Y	Y	Y	Y	Y	Y	Y	U	U	Y	Low
Rezel-Potts 2022	Y	N	U	Y	Y	Y	Y	Y	Y	NA	Y	Moderate
Roessler 2022	Y	N	U	Y	Y	Y	U	Y	U	Y	U	Moderate
Taquet 2022	Y	N	Y	Y	Y	Y	Y	Y	Y	U	Y	Moderate
Taquet 2021	Y	N	U	Y	Y	Y	Y	N	U	U	Y	High
Tartof 2022	Y	Y	U	Y	Y	U	Y	Y	Y	NA	Y	Low
Wang 2022a	Y	N	Y	Y	Y	Y	Y	Y	U	U	Y	Moderate
Wang 2022b	Y	Y	Y	Y	Y	Y	Y	Y	Y	NA	Y	Low
Westman 2022	Y	N	Y	Y	Y	Y	Y	U	Y	NA	Y	Moderate
Xie 2022a	Y	N	Y	Y	Y	Y	Y	U	Y	NA	Y	Moderate
Xie 2022b	Y	N	Y	Y	Y	Y	Y	U	U	U	Y	Moderate
Xu 2022	Y	N	Y	Y	Y	Y	Y	U	U	U	Y	Moderate
Zarifkar 2022	Y	Y	Y	Y	U	U	Y	Y	U	U	U	Moderate

N: no; NA: not applicable; U: unsure; Y: yes.

Questions:

1. Were the two groups similar and recruited from the same population?

2. Were the exposures measured similarly to assign people to both exposed and unexposed groups?*

3. Was the exposure measured in a valid and reliable way?

4. Were confounding factors identified?

5. Were strategies to deal with confounding factors stated?

6. Were the groups/participants free of the condition/diagnosis of interest at the start of the study (or at the moment of exposure)?

7. Were the outcomes measured in a valid and reliable way?

8. Was the follow up time reported and sufficient to be long enough for outcomes to occur?

9. Was follow up complete, and if not, were the reasons for loss to follow up described and explored

10. Were strategies to address incomplete follow up utilized?

11. Was appropriate statistical analysis used?

*Most studies got “No” for this question because they relied on the absence of a positive SARS-CoV-2 test/diagnosis to identify the control group (i.e. the control group was not tested and we considered this differential ascertainment in exposure).

Table 3. Summary of Findings for new diagnoses of chronic conditions after SARS-CoV-2 infection.

Outcome	Subgroup Number of Studies	Relative findings HR (95% CI)	Conclusion Certainty for relative findings	Excess cases per 1000 people over 6 monthss (95% CI)
Cardiovascular disorders
1. Any cardiovascular disorder	Inpatients, 18–64 y 1 study	4.30 (1.93–9.57)*	Small-to-moderate increase Low^a,b	11.87 (3.35–30.82)
	Inpatients, ≥ 65 y 1 study	2.90 (2.26–3.72)	Large increase Low^a,b	45.79 (30.36–65.55)
	Outpatients/mixed, < 18y 2 studies	1.16 (1.12–1.20)	Little-to-no difference Low ^b,c,1	NE
	Outpatients/mixed, 18–64 y 4 studies	1.62 (1.21–2.17)	Small-to-moderate increase Moderate ^d	1.29 (0.44–2.43)
	Outpatients/mixed, ≥ 65 y 3 studies	1.82 (1.57–2.13)	Small-to-moderate increase High	12.41 (8.62–17.1)
2. Acute coronary disease	Outpatients/mixed, < 18y 1 study	3.32 (0.42–26.23)	Very Low ^b,D	NE
	Outpatients/mixed, 18–64 y 4 studies	1.54 (1.16–2.06)	Small-to-moderate increase Moderate ^d	0.53 (0.16–1.04)
	Outpatients/mixed, ≥ 65 y 3 studies	1.79 (1.52–2.10)	Small-to-moderate increase High	6.23 (4.1–8.67)
3. Arrhythmias/ dysrhythmias	Outpatients/mixed, < 18y 2 studies	1.21 (1.02–1.44)	Little-to-no difference Moderate ^d	NE
	Outpatients/mixed, 18–64 y 4 studies	1.69 (1.46–1.96)	Small-to-moderate increase Moderate ^b	3.88 (2.59–5.4)
	Outpatients/mixed, ≥ 65 y 3 studies	1.83 (1.65–2.02)	Small-to-moderate increase High	12.56 (9.84–15.43)
4. Cardiomyopathy	Outpatients/mixed, 18–64 y 2 studies	2.81 (2.31–3.42)	Large increase High	1.26 (0.91–1.69)
	Outpatients/mixed, ≥ 65 y 2 studies	1.90 (1.16–3.13)	Small-to-moderate increase Moderate ^d	6.19 (1.1–14.65)
5. Heart failure	Outpatients/mixed, < 18y 1 study	0.56 (0.08–3.92)	Very Low ^b,D	NE
	Outpatients/mixed, 18–64 y 3 studies	2.07 (1.71–2.52)*	Small-to-moderate increase High	0.92 (0.61–1.3)
	Outpatients/mixed, ≥ 65 y 2 studies	2.01 (1.77–2.27)*	Small-to-moderate increase High	12.77 (9.73–16.05)
6. Hypertension	Outpatients/mixed, 18–64 y 1 study	1.70 (1.55–1.87)	Small-to-moderate increase Moderate ^b	6.45 (5.07–8.02)
	Outpatients/mixed, ≥ 65 y 1 study	1.70 (1.36–2.13)	Small-to-moderate increase Moderate ^b	3.6 (1.85–5.81)
Chronic kidney disease
7. Any chronic kidney disease	Inpatients, 18–64 y 1 study	3.50 (2.65–4.63)	Large increase Low ^a,b	5.22 (3.44–7.57)
	Inpatients, ≥ 65 y 1 study	2.04 (1.00–4.13)	Very low ^a,b,d	NE
	Outpatients/mixed, < 18 y 1 study	1.07 (0.94–1.21)	Little-to-no difference Moderate ^b	NE
	Outpatients/mixed, 18–64 y 1 study	1.60 (1.29–1.98)	Small-to-moderate increase Moderate ^b	1.33 (0.64–2.17)
	Outpatients/mixed, ≥ 65 y 1 study	1.36 (1.21–1.53)	Small-to-moderate increase Low ^b,d	6.96 (4.06–10.25)
Diabetes
8. Any diabetes	Inpatients, 18–64 y 1 study	1.70 (1.60–1.81)	Small-to-moderate increase Low ^a,b	14.18 (12.15–16.4)
	Inpatients, ≥ 65 y 1 study	1.46 (1.12–1.89)	Very low ^a,b,d	NE
	Outpatients/mixed, < 18y 3 studies	1.05 (0.78–1.40)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, 18–64 y 4 studies	1.27 (1.07–1.52)	Small-to-moderate increase Low ^b,d	3.1 (0.8–5.97)
	Outpatients/mixed, ≥ 65 y 2 studies	1.65 (1.21–2.24)	Small-to-moderate increase Moderate ^d	14.43 (4.66–27.53)
9. Type 1	Outpatients/mixed, < 18y 2 studies	1.23 (1.13–1.33)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, 18–64 y 1 study	0.54 (0.32–0.89)	Very Low ^b,c,2,d	NE
10. Type 2	Outpatients/mixed, < 18y 2 studies	1.17 (1.11–1.23)	Little-to-no difference Moderate ^b	NE
	Outpatients/mixed, 18–64 y 2 studies	1.34 (0.72–2.47)	Small-to-moderate increase Low ^b,d	0.92 (−0.75–3.96)
	Outpatients/mixed, ≥ 65 y 1 study	1.96 (1.60–2.40)	Small-to-moderate increase Moderate ^b	5.9 (3.69–8.61)
Mental disorders
11. Any mental disorder	Outpatients/mixed, < 18y 6 studies	1.06 (0.88–1.28)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, 18–64 y 7 studies	1.35 (1.22–1.49)	Small-to-moderate increase Low ^b,d	9.04 (5.68–12.66)
	Outpatients/mixed, ≥ 65 y 7 studies	1.54 (1.34–1.76)	Small-to-moderate increase Moderate ^b	21.12 (13.3–29.73)
12. Anxiety/anxiety disorders	Outpatients/mixed, < 18y 4 studies	0.95 (0.83–1.09)	Little-to-no difference High	NE
	Outpatients/mixed, 18–64 y 3 studies	1.08 (0.94–1.25)	Little-to-no difference High	NE
	Outpatients/mixed, ≥ 65 y 2 studies	1.04 (0.87–1.26)	Little-to-no difference High	NE
13. Depression/mood disorders	Outpatients/mixed, < 18y 3 studies	1.02 (0.78–1.32)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, 18–64 y 3 studies	1.06 (0.98–1.15)	Little-to-no difference Moderate ^b	NE
	Outpatients/mixed, ≥ 65 y 2 studies	1.17 (1.12–1.22)	Little-to-no difference Moderate ^d	NE
14. Psychosis/psychotic disorders	Outpatients/mixed, < 18y 2 studies	0.65 (0.07–6.56)	Very Low ^B,d	NE
	Outpatients/mixed, 18–64 y 1 study	1.18 (1.08–1.29)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, ≥ 65 y 2 studies	1.89 (0.97–3.66)	Small-to-moderate increase Moderate ^d	1.27 (−0.04–3.79)
15. Trauma and stress disorders	Outpatients/mixed, < 18y 1 study	1.71 (1.42–2.06)	Small-to-moderate increase Moderate ^b	54.67 (32.34–81.62)
	Outpatients/mixed, 18–64 y 1 study	1.42 (1.09–1.85)	Small-to-moderate increase Low ^b,d	0.61 (0.13–1.23)
Musculoskeletal disorders
16. Any musculoskeletal disorder	Outpatients/mixed, < 18y 2 studies	1.28 (0.65–2.55)	Very low ^b,c,3,d	NE
17. Myoneural junction/muscle disease	Outpatients/mixed, < 18y 1 study	1.90 (1.19–3.03)	Small-to-moderate increase Low ^b,d	0.13 (0.03–0.29)
	Outpatients/mixed, 18–64 y 1 study	1.88 (1.71–2.07)	Small-to-moderate increase Moderate ^b	0.7 (0.57–0.86)
	Outpatients/mixed, ≥ 65 y 1 study	1.82 (1.61–2.05)	Small-to-moderate increase Moderate ^b	1.72 (1.28–2.21)
Neurological disorders
18. Any neurological disorder	Outpatients/mixed, < 18y 6 studies	1.29 (1.01–1.65)	Small-to-moderate increase Low ^b,d	11.27 (8.38–14.43)
	Outpatients/mixed, 18–64 y 7 studies	1.55 (0.85–2.84)	Small-to-moderate increase Low ^b,d	4.83 (−1.32–16.16)
	Outpatients/mixed, ≥ 65 y 9 studies	1.40 (1.22–1.62)	Very low ^b,c,4,d	NE
19. Chronic fatigue syndrome	Outpatients/mixed, < 18y 2 studies	2.46 (1.89–3.19)*	Small-to-moderate increase Moderate ^b	0.63 (0.38–0.95)
	Outpatients/mixed, 18–64 y 1 study	2.03 (1.34–3.06)*	Small-to-moderate increase Low ^a,b	1.94 (0.64–3.88)
	Outpatients/mixed, ≥ 65 y 1 study	1.12 (1.01–1.24)	Little-to-no difference Low ^a,b	NE
20. Communication and motor disorders	Outpatients/mixed, < 18y 3 studies	1.19 (1.08–1.30)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, 18–64 y 3 studies	1.13 (0.73–1.75)	Very low ^b,D	NE
	Outpatients/mixed, ≥ 65 y 3 studies	1.28 (1.14–1.43)	Small-to-moderate increase Moderate ^d	0.15 (0.07–0.23)
21. Dementia/mild cognitive disorder	Inpatients, 18–64 y 1 study	0.98 (0.69–1.39)	Very low ^b,D	NE
	Inpatients, ≥ 65 y 1 study	6.17 (0.14–279.99)	Very low ^b,D	NE
	Outpatients/mixed, 18–64 y 6 studies	2.55 (1.27–5.13)*	Small-to-moderate increase Moderate ^b	0.61 (0.11–1.61)
	Outpatients/mixed, ≥ 65 y 8 studies	1.58 (1.37–1.82)	Small-to-moderate increase Moderate ^b	2.11 (1.34–2.98)
22. Encephalopathy	Outpatients/mixed, 18–64 y 1 study	6.26 (4.02–9.75)	Large increase Moderate ^b	1.83 (1.05–3.05)
	Outpatients/mixed, ≥ 65 y 1 study	3.36 (2.87–3.93)	Large increase Moderate ^b	19.9 (15.77–24.71)
23. Epilepsy	Outpatients/mixed, < 18y 2 studies	1.09 (0.61–1.93)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, 18–64 y 3 studies	0.97 (0.70–1.36)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, ≥ 65 y 3 studies	1.40 (1.11–1.77)	Small-to-moderate increase Moderate ^d	1.2 (0.33–2.31)
24. Guillian-Barre syndrome	Outpatients/mixed, < 18y 1 study	2.20 (0.88–5.50)*	Small-to-moderate increase Low ^b,d	0.05 (0–0.17)
	Outpatients/mixed, 18–64 y 3 studies	1.09 (0.91–1.32)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, ≥ 65 y 3 studies	1.13 (0.90–1.43)	Little-to-no difference Low ^b,d	NE
25. Migraine	Outpatients/mixed, 18–64 y 1 study	1.29 (1.12–1.48)	Small-to-moderate increase Low ^b,d	1.53 (0.63–2.54)
	Outpatients/mixed, ≥ 65 y 1 study	1.26 (1.03–1.55)	Small-to-moderate increase Low ^b,d	1.92 (0.22–4.06)
26. Multiple sclerosis	Outpatients/mixed, 18–64 y 1 study	0.76 (0.35–1.65)	Very low ^b,D	NE
	Outpatients/mixed, ≥ 65 y 1 study	2.36 (0.88–6.31)*	Small-to-moderate increase Low ^b,d	0.13 (−0.01–0.51)
27. Nerve disorders	Outpatients/mixed, < 18y 2 studies	1.15 (0.50–2.63)	Very low ^b,c,5,d	NE
	Outpatients/mixed, 18–64 y 3 studies	1.32 (0.95–1.83)	Very low ^b,c,5,d	NE
	Outpatients/mixed, ≥ 65 y 3 studies	1.10 (0.77–1.56)	Very low ^b,c,5,d	NE
Respiratory disorders
28. Any respiratory disorder	Inpatients, 18–64 y 1 study	10.50 (9.65–11.43)	Large increase Low ^a,b	168.04 (153.01–184.49)
	Inpatients, ≥ 65 y 1 study	6.86 (3.06–15.39)	Large increase Low ^a,b	385.92 (135.66–947.68)
	Outpatients/mixed, < 18y 2 studies	1.25 (0.68–2.29)	Small-to-moderate increase Low ^D	NE (no control rate data available)
	Outpatients/mixed, 18–64 y 1 study	8.94 (5.42–14.73)	Large increase Low ^b,c,6	2.82 (1.57–4.88)
	Outpatients/mixed, ≥ 65 y 1 study	3.65 (2.95–4.51)	Large increase Low ^b,c,6	10.84 (7.98–14.36)
29. Asthma	Outpatients/mixed, < 18y 1 study	1.00 (0.99–1.01)	Little-to-no difference Moderate ^b	NE
30. Interstitial lung disease	Outpatients/mixed, 18–64 y 1 study	7.71 (4.94–12.04)	Large increase Moderate ^b	2.38 (1.4–3.92)
	Outpatients/mixed, ≥ 65 y 1 study	3.07 (2.44–3.87)	Large increase Moderate ^b	8.47 (5.89–11.74)
31. Respiratory failure	Outpatients/mixed, 18–64 y 1 study	12.85 (6.39–25.84)	Large increase Moderate ^b	1.74 (0.79–3.66)
	Outpatients/mixed, ≥ 65 y 1 study	4.53 (3.50–5.87)	Large increase Moderate ^b	10.52 (7.45–14.51)
Stroke
32. Any stroke	Outpatients/mixed, < 18y 4 studies	1.31 (0.95–1.81)	Small-to-moderate increase Moderate ^d	0.03 (0–0.08)
	Outpatients/mixed, 18–64 y 7 studies	1.19 (1.01–1.40)	Little-to-no difference Low ^b,d	NE
	Outpatients/mixed, ≥ 65 y 5 studies	1.23 (1.00–1.51)	Little-to-no difference Low ^b,d	NE
33. Haemorrhagic stroke	Outpatients/mixed, 18–64 y 1 study	2.59 (1.41–4.75)*	Small-to-moderate increase Moderate ^b	0.38 (0.1–0.9)
	Outpatients/mixed, ≥ 65 y 1 study	2.04 (1.68–2.47)*	Small-to-moderate increase Moderate ^b	6.83 (4.46–9.65)
34. Ischaemic stroke	Outpatients/mixed, < 18y 1 study	1.89 (1.15–3.10)	Small-to-moderate increase Low ^b,d	0.22 (0.04–0.53)
	Outpatients/mixed, 18–64 y 3 studies	0.84 (0.51–1.37)	Very low ^b,D	NE
	Outpatients/mixed, ≥ 65 y 3 studies	0.98 (0.65–1.49)	Very low ^b,D	NE
35. Transient ischaemic attack	Outpatients/mixed, 18–64 y 1 study	1.45 (1.19–1.76)	Small-to-moderate increase Low ^b,d	NE (no control rate data available)
	Outpatients/mixed, ≥ 65 y 1 study	1.63 (1.39–1.91)	Small-to-moderate increase Moderate ^b	NE (no control rate data available)

CI: confidence interval; HR: hazard ratio; NE: not estimated.

GRADE legend: *Rated as Small-to-moderate effect for greater certainty due to less concern around lack of precision in the effect estimate; A = ROB, B = lack of consistency (including >80% contribution to estimate from 1 study), C = Indirectness (reasons in footnotes), D = imprecision

Lowercase and capital letters represent downrating that domain for one or two steps, respectively. Conclusions are reported only for outcomes with at least Low certainty.

Footnotes:

1 Largest contribution to estimate (>99%) from Kompaniyets, which has only one outcome in this category (cardiac dysrhythmias)

2 Concerns about indirectness because of age (i.e. Type 1 DM is very rare in individuals >30 years)

3 one of two studies reporting any MSK outcome only reported on a single condition (Myoneural junction/muscle disease)

4 three out of nine studies (35.6% weight) contributing to this outcome report only on dementia

5 “nerve disorders” were rarely well defined by included studies

6 Composite composed only of chronic respiratory failure and interstitial lung disease, therefore may not be generalizable to other respiratory disorders (E.g. COPD).

Note: Chevinksy 2021 reported on 31 different conditions across 7 categories, but did not stratify results for adults (≥18 y; ∼15% of sample was ≥65 y), and reported broad results for children (<18 y) stating “Children with COVID-19 were not more likely to experience new diagnoses than children without COVID-19.” Since no effect size or variance was reported for children, this study was not included in the meta-analysis. Despite attempts to contact the authors, we were unable to obtain more detailed paediatric results.

Table 4. Summary of time-varying effects and subgroup analyses by variant in a systematic review of new diagnoses of chronic conditions after SARS-CoV-2 infection.

Study	Age group	Conditions reported	Time varying effects	Effects across Variants
Rezel-Potts 2022 [45]	18–64 y	Cardiovascular disease, diabetes	For both cardiovascular disease and diabetes, IRR was highest at 4–7 weeks, decreasing over time to IRR ∼1 by 24 weeks.	Not reported
Taquet 2022 [47]	<18 y, 18–64 y, ≥ 65 y	Many	Outcomes fell into three categories: (1) within 2 years, HRs have returned to baseline (e.g. mood disorder, anxiety disorder, and ischaemic stroke) and cumulative incidence equalizes between cohorts; (2) HRs have returned to baseline within 2 years but equal cumulative incidence was not reached (i.e. myoneural junction or muscle disease); (3) HRs remained greater than 1 at the end of the follow-up period and new diagnoses are being made more frequently after COVID-19 diagnosis than after a diagnosis of another respiratory infection up to 2 years after the index event (e.g. dementia, psychotic disorders, epilepsy). These different risk trajectories were broadly similar in children, adults, and older adults.	Alpha vs. Delta vs. Omicron. Risk profiles differed across variants. Alpha: 6-month HRs did not notably change from before to after emergence of Alpha. Delta: Increased 6-month HRs of anxiety disorders, insomnia, cognitive deficit, epilepsy or seizures, and ischaemic strokes, but a lower risk of dementia, were observed in those diagnosed after the emergence of the delta variant compared to those diagnosed before. These risks were compounded by an increased risk of death. Omicron: After Omicron, patients were at an increased risk (over 140 days of follow-up) of dementia, mood disorders, and nerve, nerve root, and plexus disorders, and at a broadly similar risk of most other outcomes. All risks were largely offset by a reduced risk of death after the emergence of omicron. The authors concluded: “The decreased composite risks of death and neurological or psychiatric sequelae are reassuring for patients. However, the ongoing risk of individual outcomes indicates that health services will likely continue to face a similar rate of these post-COVID-19 diagnoses even with SARS-CoV-2 variants that lead to otherwise less severe disease.”

HR: hazard ratio; IRR: incidence rate ratio.

Abel KM, Carr MJ, Ashcroft DM, et al. Association of SARS-CoV-2 infection with psychological distress, psychotropic prescribing, fatigue, and sleep problems among UK primary care patients. JAMA Network Open. 2021;4(11):e2134803.

 PubMed Web of Science ®Google Scholar

Ayoubkhani D, Khunti K, Nafilyan V, et al. Post-COVID syndrome in individuals admitted to hospital with COVID-19: retrospective cohort study. BMJ (Clinical Research ed). 2021;372:n693.

 PubMedGoogle Scholar

Bohlken J, Weber K, Riedel Heller  S, et al. Mild cognitive disorder in post-COVID-19 syndrome: a retrospective cohort study of 67,000 primary care post-COVID patients. Journal of Alzheimer's Disease Reports. 2022;6(1):297–305.

 PubMedGoogle Scholar

Chevinsky JR, Tao G, Lavery AM, et al. Late conditions diagnosed 1-4 months following an initial coronavirus disease 2019 (COVID-19) encounter: a matched-cohort study using inpatient and outpatient administrative data-United States, 1 March-30 June 2020. Clin Infect Dis. 2021 Jul 15;73(Suppl 1):S5–S16.

 PubMedGoogle Scholar

Cohen K, Ren S, Heath K, et al. Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post-acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ (Clinical Research ed). 2022;376:e068414.

 PubMedGoogle Scholar

Daugherty SE, Guo Y, Heath K, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ (Clinical Research ed). 2021;373:n1098.

 PubMedGoogle Scholar

Donnachie E, Hapfelmeier A, Linde K, et al. Incidence of post-COVID syndrome and associated symptoms in outpatient care in Bavaria, Germany: a retrospective cohort study using routinely collected claims data. BMJ Open. 2022;12(9):e064979.

 PubMed Web of Science ®Google Scholar

Jacob L, Koyanagi A, Smith L, et al. No significant association between COVID-19 diagnosis and the incidence of depression and anxiety disorder? A retrospective cohort study conducted in Germany. J Psychiatr Res. 2022;147:79–84.

 PubMed Web of Science ®Google Scholar

Kompaniyets L, Bull-Otterson L, Boehmer TK, et al. Post-COVID-19 symptoms and conditions Among children and adolescents - United States, march 1, 2020-January 31, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(31):993–999.

 PubMedGoogle Scholar

Park HY, Song I-A, Lee SH, et al. Prevalence of mental illness among COVID-19 survivors in South Korea: nationwide cohort. BJPsych Open. 2021;7(6):e183.

 PubMedGoogle Scholar

Pietropaolo M, Hotez P, Giannoukakis N. Incidence of an insulin-requiring hyperglycemic syndrome in SARS CoV-2-infected young individuals: Is it type 1 diabetes? Diabetes. 2022;71(12):2656–2663.

 PubMedGoogle Scholar

Qureshi AI, Baskett WI, Huang W, et al. New-Onset dementia among survivors of pneumonia associated with severe acute respiratory syndrome coronavirus 2 infection. Open Forum Infect Dis. 2022;9(4):ofac115.

 PubMed Web of Science ®Google Scholar

Rao S, Lee GM, Razzaghi H, et al. Clinical features and burden of postacute sequelae of SARS-CoV-2 infection in children and adolescents. JAMA Pediatr. 2022;176(10):1000–1009.

 PubMed Web of Science ®Google Scholar

Rezel-Potts E, Douiri A, Sun X, et al. Cardiometabolic outcomes up to 12 months after COVID-19 infection. A matched cohort study in the UK. PLoS Med 2022;19(7):e1004052.

 PubMed Web of Science ®Google Scholar

Roessler M, Tesch F, Batram M, et al. Post-COVID-19-associated morbidity in children, adolescents, and adults: a matched cohort study including more than 157,000 individuals with COVID-19 in Germany. PLoS Med. 2022;19(11):e1004122.

 PubMed Web of Science ®Google Scholar

Tartof SY, Malden DE, Liu IA, et al. Health care utilization in the 6 months following SARS-CoV-2 infection. JAMA Netw Open. 2022;5(8):e2225657.

 PubMed Web of Science ®Google Scholar

Taquet M, Sillett R, Zhu L, et al. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry. 2022;9(10):815–827.

 PubMed Web of Science ®Google Scholar

Taquet M, Luciano S, Geddes JR, et al. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psychiatry. 2021;8(2):130–140.

 PubMed Web of Science ®Google Scholar

Wang L, Davis PB, Volkow ND, et al. Association of COVID-19 with New-onset Alzheimer's disease. Journal of Alzheimer's Disease: Jad. 2022;89(2):411–414.

 PubMed Web of Science ®Google Scholar

Wang W, Wang C-Y, Wang S-I, et al. Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated population: A retrospective cohort study from the TriNetX US collaborative networks. EClinicalMedicine. 2022;53:101619.

 PubMedGoogle Scholar

Westman G, Zelano J. Epilepsy diagnosis after COVID-19: A population-wide study. Seizure. 2022;101:11–14.

 PubMed Web of Science ®Google Scholar

Xie Y, Al-Aly Z. Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol. 2022;10(5):311–321.

 PubMed Web of Science ®Google Scholar

Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of COVID-19. Nat Med 2022;28(3):583–590.

 PubMed Web of Science ®Google Scholar

Xu E, Xie Y, Al-Aly  Z. Long-term neurologic outcomes of COVID-19. Nat Med. 2022;28:2406–2415.

 PubMed Web of Science ®Google Scholar

Zarifkar P, Peinkhofer C, Benros ME, et al. Frequency of neurological diseases after COVID-19, influenza A/B and bacterial pneumonia. Front Neurol. 2022;13:904796.

 PubMed Web of Science ®Google Scholar

Data availability statement

Data are available from the authors on reasonable request.