EHI to Identify Possible COVID-19 Sequelae

Abstract and Introduction

Abstract

Ongoing symptoms might follow acute COVID-19. Using electronic health information, we compared pre– and post–COVID-19 diagnostic codes to identify symptoms that had higher encounter incidence in the post–COVID-19 period as sequelae. This method can be used for hypothesis generation and ongoing monitoring of sequelae of COVID-19 and future emerging diseases.

Introduction

SARS-CoV-2 causes acute COVID-19 and may cause post–COVID-19 conditions, which include a range of long-term sequelae.^[1,2] Review of multiple studies describes ongoing symptoms after acute COVID-19.^[3] Post–COVID-19 conditions might include symptoms of nonspecific chest pain, fatigue, and malaise, as well as cardiomyopathy, renal failure, lung disease, and venous thromboembolism. Identifying possible sequelae of an emerging disease has traditionally required aggregating clinical experiences; this approach might miss sequelae that are rare or where the increase above baseline is not obvious.^[4]

Large electronic health information databases might aid in detecting these early signals, especially when potential sequelae events are temporally and geographically dispersed. The International Classification of Diseases, 10th revision (ICD-10), code for post–COVID-19 conditions was not available for use in the United States until October 2021; thus, examining other diagnosis codes is needed to infer potential sequelae.^[5] We evaluated feasibility of a method comparing pre– and post–COVID-19 diagnosis healthcare codes to identify possible sequelae from a large national database of healthcare encounters.

Table. Diagnostic codes reported during post–COVID-19 interval with increased rate >60 d after acute illness relative to pre–COVID-19 baseline rate, by interval from index date, from large administrative all-payer database, United States, January 2019–December 2020*
Diseases and codes	Rate increase relative to pre–COVID-19 rate (SE)†	Post–COVID-19 rate, encounters/1,000 person-months
60–89 d	90–119 d	120–149 d	60–89 d	90–119 d	120–149 d
Certain infectious and parasitic diseases
B97.21: SARS-associated coronavirus as the cause of diseases classified elsewhere	28.7 (12.8)	31.9 (15.6)	82.2 (39.5)	0.22	0.24	0.63
B94.8: Sequelae of other specified infectious and parasitic diseases	15.4 (4.5)	17 (5.1)	11.6 (4.2)	0.26	0.29	0.20
A41.53: Sepsis due to Serratia	6 (3.9)	NS	NS	0.60	NS	NS
A41.89: Other specified sepsis	2.8 (0.5)	NS	NS	0.69	NS	NS
B34.2: Coronavirus infection, unspecified	2 (0.6)	2.4 (0.7)	NS	0.24	0.29	NS
R65.21: Severe sepsis with septic shock	1.5 (0.2)	NS	NS	1.29	NS	NS
Diseases of blood and blood-forming organs and certain disorders involving the immune mechanism
D84.821: Immunodeficiency due to drugs	7.9 (6.0)	NS	NS	0.30	NS	NS
Diseases of the circulatory system
B33.24: Viral cardiomyopathy	9.8 (8.8)	NS	NS	0.30	NS	NS
I46.8: Cardiac arrest due to other underlying condition	4.8 (2.3)	3.5 (1.9)	NS	0.70	0.50	NS
I46.9: Cardiac arrest, cause unspecified	4.6 (0.9)	3.7 (0.9)	4.5 (1.1)	0.40	0.32	0.38
I40.0: Infective myocarditis	NS	12.6 (10.6)	NS	NS	0.40	NS
Diseases of the digestive system
K20.91: Esophagitis, unspecified with bleeding	19.8 (18.4)	NS	NS	0.30	NS	NS
K21.00: Gastro-esophageal reflux disease with esophagitis, without bleeding	5.7 (1.3)	6.1 (1.5)	5.7 (1.7)	0.29	0.31	0.29
K20.90: Esophagitis, unspecified without bleeding	3.1 (1.4)	5.8 (2.3)	NS	0.70	0.13	NS
K00.7: Teething syndrome	NS	4 (2.3)	NS	NS	0.50	NS
Diseases of the genitourinary system
N18.31: Chronic kidney disease, stage 3a	4 (1.4)	5.1 (1.9)	6.4 (2.2)	0.14	0.18	0.22
N18.30: Chronic kidney disease, stage 3 unspecified	3.6 (0.3)	3.8 (0.4)	4.2 (0.5)	1.83	1.91	2.13
N18.32: Chronic kidney disease, stage 3b	2.5 (1.0)	3.2 (1.2)	5.1 (1.9)	0.90	0.12	0.19
Diseases of the musculoskeletal system and connective tissue
M62.59: Muscle wasting and atrophy, not elsewhere classified, multiple sites	NS	4.1 (2.1)	NS	NS	0.10	NS
M65.071: Abscess of tendon sheath, right ankle and foot	NS	NS	280.3 (550.3)	NS	NS	0.10
Diseases of the nervous system
G62.81: Critical illness polyneuropathy	11.8 (6.8)	9.1 (6.8)	NS	0.70	0.50	NS
G93.3: Postviral fatigue syndrome	6.8 (2.5)	4.2 (2.1)	NS	0.12	0.70	NS
G72.81: Critical illness myopathy	5 (1.5)	NS	NS	0.30	NS	NS
R51.9: Headache, unspecified	2.6 (0.3)	3.9 (0.3)	3.9 (0.4)	1.47	2.23	2.23
Diseases of the respiratory system
J12.81: Pneumonia due to SARS-associated coronavirus	8.5 (3.6)	NS	NS	0.90	NS	NS
J80: Acute respiratory distress syndrome	7.4 (2.9)	3.9 (1.7)	NS	0.32	0.17	NS
J95.851: Ventilator associated pneumonia	5.2 (2.4)	4 (2.1)	NS	0.90	0.70	NS
J12.89: Other viral pneumonia	NS	16.1 (2.6)	11 (2.0)	NS	1.33	0.91
Diseases of skin and subcutaneous tissue
L65.9: Nonscarring hair loss, unspecified	2.4 (0.5)	3.5 (0.7)	2.3 (0.6)	0.36	0.54	0.35
L89.153: Pressure ulcer of sacral region, stage 3	1.7 (0.4)	NS	NS	0.42	NS	NS
L89.154: Pressure ulcer of sacral region, stage 4	1.6 (0.3)	NS	NS	0.68	NS	NS
Endocrine, nutritional, and metabolic diseases
E87.71: Transfusion associated circulatory overload	4.9 (3.0)	NS	NS	0.40	NS	NS
Mental, behavioral, and neurodevelopmental disorders
F10.139: Alcohol abuse with withdrawal, unspecified	8.8 (7.6)	NS	NS	0.30	NS	NS
Neoplasms
C83.90: Non-follicular (diffuse) lymphoma, unspecified, unspecified site	411 (807)	272.6 (535.2)	NS	0.14	0.90	NS
Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified
R74.01: Elevation of liver transaminase levels	4.8 (1.2)	5 (1.4)	6.5 (1.9)	0.21	0.21	0.28

Table. Diagnostic codes reported during post–COVID-19 interval with increased rate >60 d after acute illness relative to pre–COVID-19 baseline rate, by interval from index date, from large administrative all-payer database, United States, January 2019–December 2020*

Diseases and codes

Rate increase relative to pre–COVID-19 rate (SE)†

Post–COVID-19 rate, encounters/1,000 person-months

60–89 d

90–119 d

120–149 d

60–89 d

90–119 d

120–149 d

Certain infectious and parasitic diseases

B97.21: SARS-associated coronavirus as the cause of diseases classified elsewhere

28.7 (12.8)

31.9 (15.6)

82.2 (39.5)

0.22

0.24

0.63

B94.8: Sequelae of other specified infectious and parasitic diseases

15.4 (4.5)

17 (5.1)

11.6 (4.2)

0.26

0.29

0.20

A41.53: Sepsis due to Serratia

6 (3.9)

0.60

A41.89: Other specified sepsis

2.8 (0.5)

0.69

B34.2: Coronavirus infection, unspecified

2 (0.6)

2.4 (0.7)

0.24

0.29

R65.21: Severe sepsis with septic shock

1.5 (0.2)

1.29

Diseases of blood and blood-forming organs and certain disorders involving the immune mechanism

D84.821: Immunodeficiency due to drugs

7.9 (6.0)

0.30

Diseases of the circulatory system

B33.24: Viral cardiomyopathy

9.8 (8.8)

0.30

I46.8: Cardiac arrest due to other underlying condition

4.8 (2.3)

3.5 (1.9)

0.70

0.50

I46.9: Cardiac arrest, cause unspecified

4.6 (0.9)

3.7 (0.9)

4.5 (1.1)

0.40

0.32

0.38

I40.0: Infective myocarditis

12.6 (10.6)

0.40

Diseases of the digestive system

K20.91: Esophagitis, unspecified with bleeding

19.8 (18.4)

0.30

K21.00: Gastro-esophageal reflux disease with esophagitis, without bleeding

5.7 (1.3)

6.1 (1.5)

5.7 (1.7)

0.29

0.31

0.29

K20.90: Esophagitis, unspecified without bleeding

3.1 (1.4)

5.8 (2.3)

0.70

0.13

K00.7: Teething syndrome

4 (2.3)

0.50

Diseases of the genitourinary system

N18.31: Chronic kidney disease, stage 3a

4 (1.4)

5.1 (1.9)

6.4 (2.2)

0.14

0.18

0.22

N18.30: Chronic kidney disease, stage 3 unspecified

3.6 (0.3)

3.8 (0.4)

4.2 (0.5)

1.83

1.91

2.13

N18.32: Chronic kidney disease, stage 3b

2.5 (1.0)

3.2 (1.2)

5.1 (1.9)

0.90

0.12

0.19

Diseases of the musculoskeletal system and connective tissue

M62.59: Muscle wasting and atrophy, not elsewhere classified, multiple sites

4.1 (2.1)

0.10

M65.071: Abscess of tendon sheath, right ankle and foot

280.3 (550.3)

0.10

Diseases of the nervous system

G62.81: Critical illness polyneuropathy

11.8 (6.8)

9.1 (6.8)

0.70

0.50

G93.3: Postviral fatigue syndrome

6.8 (2.5)

4.2 (2.1)

0.12

0.70

G72.81: Critical illness myopathy

5 (1.5)

0.30

R51.9: Headache, unspecified

2.6 (0.3)

3.9 (0.3)

3.9 (0.4)

1.47

2.23

Diseases of the respiratory system

J12.81: Pneumonia due to SARS-associated coronavirus

8.5 (3.6)

0.90

J80: Acute respiratory distress syndrome

7.4 (2.9)

3.9 (1.7)

0.32

0.17

J95.851: Ventilator associated pneumonia

5.2 (2.4)

4 (2.1)

0.90

0.70

J12.89: Other viral pneumonia

16.1 (2.6)

11 (2.0)

1.33

0.91

Diseases of skin and subcutaneous tissue

L65.9: Nonscarring hair loss, unspecified

2.4 (0.5)

3.5 (0.7)

2.3 (0.6)

0.36

0.54

0.35

L89.153: Pressure ulcer of sacral region, stage 3

1.7 (0.4)

0.42

L89.154: Pressure ulcer of sacral region, stage 4

1.6 (0.3)

0.68

Endocrine, nutritional, and metabolic diseases

E87.71: Transfusion associated circulatory overload

4.9 (3.0)

0.40

Mental, behavioral, and neurodevelopmental disorders

F10.139: Alcohol abuse with withdrawal, unspecified

8.8 (7.6)

0.30

Neoplasms

C83.90: Non-follicular (diffuse) lymphoma, unspecified, unspecified site

411 (807)

272.6 (535.2)

0.14

0.90

Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified

R74.01: Elevation of liver transaminase levels

4.8 (1.2)

5 (1.4)

6.5 (1.9)

0.21

0.28

Longitudinal Analysis of Electronic Health Information to Identify Possible COVID-19 Sequelae

Abstract and Introduction

Abstract

Introduction

Tables

References

Authors and Disclosures

Authors and Disclosures

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