Patients with unmet social needs are at higher risks of developing severe long COVID-19 symptoms and neuropsychiatric sequela

doi:10.21203/rs.3.rs-3779170/v1

Download PDF

Article

Patients with unmet social needs are at higher risks of developing severe long COVID-19 symptoms and neuropsychiatric sequela

https://doi.org/10.21203/rs.3.rs-3779170/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 02 Apr, 2024

Read the published version in Scientific Reports →

You are reading this latest preprint version

This study investigated long COVID of patients in the Montefiore Health System COVID-19 (CORE) Clinics in the Bronx with an emphasis on identifying health related social needs (HRSNs). We analyzed a cohort of 643 CORE patients (6/26/2020-2/24/2023) and 52,089 non-CORE COVID-19 patients. Outcomes included symptoms, physical, emotional, and cognitive function test scores obtained at least three months post-infection. Socioeconomic variables included median incomes, insurance status, and HRSNs. The CORE cohort was older age (53.38 ± 14.50 versus 45.91 ± 23.79 years old, p < 0.001), more female (72.47% vs 56.86%, p < 0.001), had higher prevalence of hypertension (45.88% vs 23.28%, p < 0.001), diabetes (22.86% vs 13.83%, p < 0.001), COPD (7.15% vs 2.28%, p < 0.001), asthma (25.51% vs 12.66%, p < 0.001), lower incomes (53.81% vs 43.67%, 1st quintile, p < 0.001), and more unmet social needs (29.81% vs 18.49%, p < 0.001) compared to non-CORE COVID-19 survivors. CORE patients reported a wide range of severe long-COVID symptoms. CORE patients with unmet HRSNs experienced more severe symptoms, worse ESAS-r scores (wellbeing, shortness of breath, anxiety, and depression), PHQ-9 scores (overall: 12.05 ± 7.07 vs 7.71 ± 6.35, p < 0.001), and GAD-7 scores (overall: 9.26 ± 6.63 vs 5.28 ± 5.72, p < 0.001) compared to CORE patients without. Patients with unmet HRSNs experienced worse long-COVID outcomes compared to those without.

Health sciences/Diseases/Infectious diseases/Viral infection

Health sciences/Risk factors

PASC

long covid

pulmonary function tests

brain imaging

chest imaging

covid symptoms

fatigue

shortness of breath

Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as long COVID, has emerged as a significant public health concern in part because of the sheer number of individuals infected by SARS-CoV-2 ^1–4. PASC includes, but are not limited to, anxiety, depression, post-traumatic stress disorder, and other neurological, psychiatric, and cognitive symptoms ^5–8.

COVID-19 has disproportionately affected marginalized communities, amplifying the inequalities they face in accessing healthcare, resources, and socioeconomic stability^9,10. Factors such as limited access to quality healthcare, higher rates of underlying health conditions, overcrowded living conditions, and employment in essential but higher-risk jobs have all contributed to the heightened impact of COVID-19 on vulnerable populations^11,12. A few studies have shown that patients with lower socioeconomic status or unmet health related social needs (HRSNs) are more likely to be infected by SARS-CoV-2 and have worse acute clinical outcomes ^13–18. These vulnerable populations are also at higher risk of developing long COVID but are less studied ¹⁹. Common HRSNs include food and housing, utilities, out of pocket healthcare costs, child/adult care, and healthcare transportation. Examining the relationship between HRSNs and PASC could shed light on the likely challenges faced by this population and could help to address the nuanced needs of individuals experiencing prolonged health consequences post-COVID infection ²⁰.

The Bronx in New York City was hit hard by the first wave of COVID-19 and by multiple subsequent surges of infection from different variants ²¹. Montefiore Health System (MHS) is the largest health care provider in Bronx County, serving a diverse patient population, including many patients with low socioeconomic status. In June 2020, Montefiore Medical Center (MMC) established two COVID-19 Recovery and Engagement (CORE) Clinics for COVID-19 survivors with protracted symptoms. A detailed evaluation protocol was implemented to assess physical, emotional, and function across the neurological and psychiatric domains for patients suspected to have long COVID.

In this paper, we reported long-COVID symptoms, physical, emotional, and cognitive function of CORE patients from June 26th, 2020 and February 24th, 2023. Outcomes were interpreted with emphasis on their relationship with socioeconomic data which included median incomes, insurance status, and HSRNs. The objective of this study was to identify how HSRNs impact long COVID symptoms incidence and severity in a diverse and underprivileged population.

Data sources

This study was approved by the Einstein IRB (IRB# 2021–13658) with a waiver of informed consent. This is a retrospective observational study of COVID-19 adult patients with protracted symptoms who were referred to MMC’s COVID-19 Recovery and Engagement (CORE) clinics. Eligible patients were at least 18 years of age who had probable or confirmed COVID-19 infection and were experiencing new or continued symptoms greater than 4 weeks after initial infection.

There were 643 patients who came to the CORE for COVID-19 related medical issues between June 26th, 2020 and February 24th, 2023. For comparison, the COVID-positive (COVID+) cohort consisted of 52,089 Montefiore patients who were still alive three months after initial COVID + diagnosis date over the same period. The date of the first positive reverse transcription polymerase chain reaction (RT-PCR) is extracted as the date of COVID-19 diagnosis. For CORE patients without positive RT-PCR results in their chart, the date of COVID-19 infection is recorded by CORE physicians in the doctor’s note and collected via chart review.

Data abstraction

De-identified health data were obtained for research after standardization to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) version 6. OMOP CDM represents healthcare data from diverse sources, which are stored in standard vocabulary concepts¹⁹, allowing for the systematic analysis of disparate observational databases, including data from the electronic medical record (EMR), administrative claims, and disease classifications systems (e.g., ICD-10, SNOWMED, LOINC, etc.). ATLAS, a web-based tool developed by the Observational Health Data Sciences and Informatics (OHDSI) community that enables navigation of patient-level, observational data in the CDM format, was used to search vocabulary concepts and facilitate cohort building. Data were subsequently exported and queried as SQLite database files using the DB Browser for SQLite (version 3.12.0). To ensure data accuracy, our team performed extensive cross validation of all major variables extracted by manual chart reviews on subsets of patients^13–18.

Demographics and comorbidities

Age, sex, BMI, combined race ethnicity, median household income quintile, and insurance status were extracted from patient EMR. Age and BMI at the time of or closest to COVID-19 diagnosis were recorded. Income data was obtained by matching patient’s zip code to median household income as reported by the census, and then assigning quintiles based on the cohorts’ combined incomes. Preexisting comorbidities included hypertension, chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus, congestive heart failure (CHF), and chronic kidney disease (CKD) that were designated by ICD10 codes at admission or prior.

COVID-19 disease severity

COVID-19 disease severity was categorized into hospitalized (general floor) and hospitalized (critically ill). All hospitalized patients admitted to the intensive care unit (ICU) or placed on invasive mechanical ventilation (IMV) were considered critically ill.

Vaccination status

The vaccination status of CORE patients at the time of COVID-19 infection was recorded by CORE physicians in the doctor’s note and collected via chart review. Vaccination status could not be collected for COVID + patients given the inconsistent coding in EPIC and large sample size requiring chart review.

Health Related Social Needs: The majority of CORE patients completed the Montefiore-Einstein Social Determinants of Health Screen (March 1, 2020 version), which is a standardized instrument developed by Health Leads Toolkit (https://healthleadsusa.org/) and adapted by Montefiore-Einstein’s Office of Community and Population Health in 2018. MHS’s screening tool is provided during routine clinical visits across the health system and is integrated into MHS’s EHR. The screener asks about the following social need categories: housing, food insecurity, utilities, health transportation, medications, child or elderly care, legal services, family stress and safety²².

Long COVID physical symptom questionnaires

All CORE patients were surveyed for the presence of various post-infection symptoms, labeled as “Symptoms Present at 1st Core Visit.” CORE patients additionally completed a revised Edmonton Symptom Assessment System (ESAS-r) where they scored various symptoms from 0 (no symptoms or best overall wellbeing) to 10 (the worst level of symptom imaginable or worst overall wellbeing). The average and standard deviation of each ESAS-r symptom severity was calculated.

Long COVID behavioral symptom questionnaire

CORE patients were assessed for depression and anxiety using the Patient Health Questionnaire (PHQ-9) Questionnaire and Generalized Anxiety Disorder (GAD-7) Questionnaire, respectively. Questionnaire results were reported as an average and standard deviation, in addition to incidence of various respective provisional diagnosis categories.

Statistical Analysis

Analysis was performed by comparing CORE patients with all other COVID-19 patients. Analysis was also performed between patients with and without unmet social needs. Analysis of group differences employed c² tests for categorical variables and unpaired t-tests for continuous variables via the statistical libraries in SPSS and RStudio, respectively. When comparing differences of categorical variables across three groups, c² tests were used to identify group differences and ad hoc pairwise tests were used to identify the specific pairwise group difference. Statistics were not adjusted for multiple comparison and no variables were controlled for due to the exploratory nature of the study. P < 0.05 was considered statistically significant.

Figure 1A displays a histogram of date of COVID-19 infection and 1st CORE visit. Relatively more CORE patients were infected early in the pandemic compared to later in the pandemic. More CORE patients visited early in the pandemic compared to later in the pandemic.

Table 1 shows the demographic, disease severity, and socioeconomic profiles of CORE and COVID + patients. Compared to the all COVID + cohort, CORE patients were older (53.38 ± 14.50 versus (vs) 45.91 ± 23.79 years old, p < 0.001), had higher BMI (31.80 ± 7.64 vs 28.34 ± 7.70, p < 0.001), and more likely to be female (72.74% vs 56.86%, p < 0.001). Except for White, not Hispanic (9.64% vs 12.42%, p = 0.033) and Hispanic (46.50% vs 39.84%, p = 0.001), there were no statistically significant differences in combined race and ethnicity (p > 0.05) between the two groups. With respect to comorbidities, CORE patients had higher proportions of hypertension (45.88% vs 23.28%, p < 0.001), COPD (7.15% vs 2.28%, p < 0.001), asthma (25.51% vs 12.66%, p < 0.001), and diabetes mellitus (22.86% vs 13.83%, p < 0.001), but no statistically significant difference in CHF or CKD (p > 0.05). CORE patients had slightly decreased hospitalization (general floor) rates (22.86% vs 23.86%, p < 0.001), but no difference in critical illness (p > 0.05). CORE patients were also primarily unvaccinated at the time of COVID-19 infection (83.67%).

Table 1

*CORE and all COVID + patient cohort profiles at diagnosis. Values reported as mean ± standard deviation (SD) or N (%). *p < 0.05, **p < 0.01, ***p < 0.001 as compared to CORE.*
	CORE (N = 643)	All COVID+ (N = 52,089)
Age, years old	53.83 ± 14.50	45.91 ± 23.79***
Female	466 (72.47%)	29,619 (56.86%)***
BMI	31.80 ± 7.64	28.34 ± 7.70***
Combined Race and Ethnicity
White, not Hispanic	62 (9.64%)	6,472 (12.42%)*
Black, not Hispanic	170 (26.44%)	14,712 (28.24%)
Hispanic	299 (46.50%)	20,751 (39.84%)**
Other	112 (17.42%)	10,026 (19.25%)
Comorbidities
Hypertension	295 (45.88%)	12,177 (23.38%)***
COPD	46 (7.15%)	1,189 (2.28%)***
Asthma	164 (25.51%)	6,595 (12.66%)***
Diabetes Mellitus	147 (22.86%)	7,205 (13.83%)***
CHF	32 (4.98%)	2,290 (4.40%)
CKD	36 (5.60%)	3,753 (7.20%)
COVID-19 Disease Severity
Hospitalized (General Floor)	147 (22.86%)	12,430 (23.86%)***
Hospitalized (Critically Ill)	50 (7.78%)	3,103 (5.96%)
Vaccination Status
Unvaccinated	538 (83.67%)
Partially Vaccinated	5 (0.78%)
Fully Vaccinated	65 (10.11%)
Fully Vaccinated with Booster	27 (4.20%)
Median Household Income Quintile
1 ($55,275.80)	346 (53.81%)	22,745 (43.67%)***
2 ($69,938.40)	151 (23.48%)	14,082 (27.03%)*
3 ($88,767.60)	82 (12.75%)	6,621 (12.71%)
4 ($115,314.60)	22 (3.42%)	2, 739 (5.26%)*
5 ($250,000)	27 (4.20%)	2, 199 (4.22%)
Insurance Status
Private	212 (32.97%)	13, 643 (26.19%)***
Medicaid	204 (31.73%)	21,364 (41.01%)***
Medicare	96 (14.93%)	10,164 (19.51%)**
Uninsured	45 (7.00%)	2,752 (5.28%)
Care Management Organization > Private	77 (11.98%)	2,068 (3.97%)***
Other	7 (1.09%)	622 (1.19%)
Unmet Social Needs	N = 369	N = 10,376
0	259 (70.19%)	8,457 (81.51%)***
1+	110 (29.81%)	1,919 (18.49%)***

With respect to socioeconomic data, CORE patients had higher proportions of 1st (lowest) quintile median household income as compared to the COVID + cohort (53.81% vs 43.67%, p < 0.001). Additionally, CORE patients were more likely to have private insurance (32.97% vs 26.19%, p < 0.001) or care management organization (11.98% vs 3.97%, p < 0.001), but also less likely to use Medicaid (31.73% vs 41.01%, p < 0.001) and Medicare (14.93% vs 19.51%, p = 0.004). Overall, there were significantly more CORE patients with unmet social needs (29.62% vs 18.49%, p < 0.001).

Figure 2 presents the HRSN questionnaire results for CORE versus COVID + groups broken down by individual unmet need. CORE patients had statistically significant greater incidence of concerns about housing quality (11.96% vs 5.57%, p < 0.001), housing situation (11.14% vs 5.02%, p < 0.001), money for food (8.97% vs 5.86%, p = 0.046), utilities shut threat (5.98% vs 3.21%, p = 0.012), and legal help (5.43% vs 2.77%, p = 0.008) as compared to the COVID + group.

The results of the long COVID physical symptom and behavioral questionnaires for CORE patients are shown in Table 2. The most common symptoms were dyspnea (47.43%), fatigue (39.04%), decreased exercise tolerance (27.84%), and brain fog/cognitive issues (27.53%). According to the ESAS-r Questionnaire, the most severe symptoms were tiredness (5.20 ± 3.20), worsened overall wellbeing (4.35 ± 2.97), and shortness of breath (4.23 ± 3.28). On average, PHQ-9 and GAD-7 questionnaires showed CORE patients experienced mild depression (8.95 ± 6.78) and mild anxiety (6.55 ± 6.21), respectively.

Table 2

Long COVID symptom questionnaire results stratified by COVID-19 disease severity. Values reported as mean ± standard deviation (SD) or N (%). * p < 0.05, ** p < 0.01, *** p < 0.001 between non-hospitalized and hospitalized (general floor). ^ p < 0.05, ^^ p < 0.01, ^^^ p < 0.001 between hospitalized (general floor) and hospitalized (critically ill). ⁺ *p < 0.05*, ⁺⁺ *p < 0.01*, ⁺⁺⁺ *p < 0.001 between non-hospitalized and hospitalized (critically ill).*
	CORE (N = 643)	Non-Hospitalized (N = 466)	Hospitalized General Floor (N = 147)	Hospitalized Critically Ill (N = 50)
Symptoms Present at 1st CORE Visit
Dyspnea	305 (47.43%)	185 (39.70%)**	80 (54.42%)^^	40 (80.00%)⁺⁺⁺
Fatigue	251 (39.04%)	163 (34.98%)	59 (40.14%)^	29 (58.00%)⁺⁺
Decreased Exercise Tolerance	179 (27.84%)	100 (21.46%)**	54 (36.73%)	25 (50.00%)⁺⁺⁺
Brain Fog/Cognitive Issues	177 (27.53%)	120 (25.75%)	39 (26.53%)	18 (36.00%)
Abnormal Smell/Taste	85 (13.22%)	66 (14.16%)	16 (10.88%)	3 (6.00%)
Cough	75 (11.66%)	47 (10.09%)	15 (10.20%)^^	13 (26.00%)⁺⁺
Chest Pain	66 (10.26%)	53 (11.37%)	9 (6.12%)	4 (8.00%)
Headache	57 (8.86%)	49 (10.52%)*	7 (4.76%)	1 (2.00%)⁺
Joint Pain	50 (7.78%)	30 (6.44%)	15 (10.20%)	5 (10.00%)
Palpitations	47 (7.31%)	30 (6.44%)	12 (8.16%)	5 (10.00%)
Back Pain	42 (6.53%)	33 (7.08%)	8 (5.44%)	1 (2.00%)
Lightheadedness/Dizziness	39 (6.07%)	27 (5.79%)	8 (5.44%)	4 (8.00%)
Post-exertional Malaise	15 (2.33%)	11 (2.36%)	4 (2.72%)	0 (0.00%)
ESAS-r Responses (scale of 0–10, best to worst)
Tiredness	5.20 ± 3.20	5.69 ± 3.30	4.81 ± 3.50	3.94 ± 3.24⁺⁺
Overall Wellbeing	4.35 ± 2.97	4.55 ± 2.82	4.30 ± 3.30	3.20 ± 3.11⁺
Shortness of Breath	4.23 ± 3.28	4.35 ± 3.30	4.26 ± 3.34	3.67 ± 2.94
Pain	3.71 ± 3.09	3.83 ± 3.12	3.95 ± 3.11^	2.39 ± 2.70⁺
Anxiety	3.57 ± 3.46	3.99 ± 3.46*	3.03 ± 3.14	2.24 ± 3.02⁺⁺
Drowsiness	3.26 ± 3.26	3.49 ± 3.32	2.96 ± 2.98	2.50 ± 2.74
Depression	2.84 ± 3.25	2.96 ± 3.23	2.93 ± 3.07	1.83 ± 2.87
Lack of Appetite	1.93 ± 2.78	2.04 ± 2.76	2.19 ± 2.73^^	0.59 ± 1.43⁺⁺
Nausea	1.07 ± 2.21	1.26 ± 2.38	0.88 ± 1.73	0.32 ± 0.99
PHQ-9 (0–27)
Overall	8.95 ± 6.78	9.47 ± 6.47	8.95 ± 7.29^	5.63 ± 6.51⁺⁺
Normal or Minimal Depression (0–4)	132 (32.92%)	67 (25.87%)*	29 (32.22%)^	119 (54.29%)⁺⁺⁺
Mild Depression (5–9)	102 (25.44%)	76 (29.34%)	18 (20.00%)	8 (22.86%)
Moderate Depression (10–14)	77 (19.20%)	60 (23.17%)	15 (16.67%)	2 (5.71%)⁺⁺
Moderately Severe Depression (15–19)	56 (13.97%)	34 (13.13%)	19 (21.11%)	3 (8.57%)
Severe Depression (20+)	34 (8.48%)	22 (8.49%)	9 (10.00%)	3 (8.57%)
GAD-7 (0–21)
Overall	6.44 ± 6.21	7.14 ± 6.10	5.63 ± 5.86	4.00 ± 5.38⁺⁺
No or Little Anxiety (0–4)	200 (50.25%)	115 (44.40%)	25 (47.17%)	13 (52.00%)⁺⁺
Mild Anxiety Disorder (5–9)	80 (20.10%)	60 (23.17%)	16 (30.19%)	4 (16.00%)
Moderate Anxiety Disorder (10–14)	60 (15.08%)	43 (16.60%)	12 (22.64%)	5 (20.00%)
Severe Anxiety Disorder (15–21)	58 (14.57%)	41 (15.83%)	0 (0.00%)	3 (12.00%)

Table 3

**(A)** demographics and **(B)** long COVID symptom questionnaire results stratified by without and with *unmet social needs in CORE patients. Values reported as mean ± standard deviation (SD) or N (%). *p < 0.05, **p < 0.01, ***p < 0.001 between groups.*
(A)	Without Unmet Needs (N = 259)	With Unmet Needs (N = 110)
Age, years old	54.06 ± 14.38	51.60 ± 12.23
Female	192 (74.13%)	77 (70.00%)
BMI	31.82 ± 7.32	33.38 ± 7.27
Combined Race and Ethnicity
White, not Hispanic	34 (13.13%)	8 (7.27%)
Black, not Hispanic	72 (27.80%)	38 (34.55%)
Hispanic	107 (41.31%)	52 (47.27%)
Other	46 (17.76%)	12 (10.91%)
Comorbidities
Hypertension	116 (44.79%)	52 (47.27%)
COPD	16 (6.18%)	10 (9.09%)
Asthma	55 (21.24%)	28 (25.45%)
Diabetes Mellitus	47 (18.15%)	24 (21.82%)
CHF	7 (2.70%)	5 (4.55%)
CKD	13 (5.02%)	6 (5.45%)
COVID-19 Disease Severity
Hospitalized (General Floor)	59 (22.78%)	31 (28.18%)
Hospitalized (Critically Ill)	20 (7.72%)	8 (7.27%)
Vaccination Status
Unvaccinated	203 (78.38%)	86 (78.18%)
Partially Vaccinated	4 (1.54%)	0 (0.00%)
Fully Vaccinated	35 (13.51%)	17 (15.45%)
Fully Vaccinated with Booster	14 (5.41%)	5 (4.55%)
Median Household Income Quintile
1 ($55,275.80)	139 (53.67%)	69 (62.73%)
2 ($69,938.40)	57 (22.01%)	22 (20.00%)
3 ($88,767.60)	35 (13.51%)	11 (10.00%)
4 ($115,314.60)	8 (3.09%)	4 (3.64%)
5 ($250,000)	15 (5.79%)	1 (0.91%)*
Insurance Status
Private	105 (40.54%)	34 (30.91%)
Medicaid	69 (26.64%)	48 (43.64%)**
Medicare	33 (12.74%)	14 (12.73%)
Uninsured	21 (8.11%)	3 (2.73%)
Care Management Organization > Private	27 (10.42%)	9 (8.18%)
Other	3 (1.16%)	1 (0.91%)

(B)	Without Unmet Needs (N = 259)	With Unmet Needs (N = 110)	P-value
Symptoms Present at 1st CORE Visit
Dyspnea	137 (52.90%)	55 (50.00%)	0.611
Fatigue	117 (45.17%)	52 (47.27%)	0.711
Decreased Exercise Tolerance	65 (25.10%)	24 (21.82%)	0.501
Brain Fog/Cognitive Issues	83 (32.05%)	47 (42.73%)	0.049
Abnormal Smell/Taste	35 (13.51%)	17 (15.45%)	0.624
Cough	32 (12.36%)	10 (9.09%)	0.366
Chest Pain	21 (8.11%)	12 (10.91%)	0.388
Headache	19 (7.34%)	10 (9.09%)	0.567
Joint Pain	23 (8.88%)	7 (6.36%)	0.418
Palpitations	24 (9.27%)	7 (6.36%)	0.358
Back Pain	19 (7.34%)	8 (7.27%)	0.983
Lightheadedness/Dizziness	17 (6.56%)	9 (8.18%)	0.579
Post-exertional Malaise	7 (2.70%)	3 (2.73%)	0.989
ESAS-r Responses (scale of 0–10, best to worst)
Tiredness	4.91 ± 3.13	5.70 ± 3.57	0.002
Overall Wellbeing	3.94 ± 2.96	5.19 ± 2.94	< 0.001
Shortness of Breath	3.90 ± 3.26	4.26 ± 3.54	0.030
Pain	3.38 ± 3.03	4.64 ± 3.08	< 0.001
Anxiety	3.03 ± 3.19	5.14 ± 3.65	< 0.001
Drowsiness	2.79 ± 3.12	4.38 ± 3.32	< 0.001
Depression	2.24 ± 2.94	4.51 ± 3.55	< 0.001
Lack of Appetite	1.65 ± 2.59	2.90 ± 3.14	< 0.001
Nausea	0.92 ± 2.06	1.52 ± 2.59	0.034
PHQ-9 (0–27)
Overall	7.71 ± 6.35	12.05 ± 7.07	< 0.001
Normal or Minimal Depression (0–4)	97 (38.34%)	19 (17.43%)	< 0.001
Mild Depression (5–9)	68 (26.88%)	22 (20.18%)	0.176
Moderate Depression (10–14)	49 (19.37%)	21 (19.27%)	0.982
Moderately Severe Depression (15–19)	24 (9.49%)	30 (27.52%)	< 0.001
Severe Depression (20+)	15 (5.93%)	17 (15.60%)	0.003
GAD-7 (0–21)
Overall	5.28 ± 5.72	9.26 ± 6.63	< 0.001
No or Little Anxiety (0–4)	177 (61.89%)	35 (31.11%)	< 0.001
Mild Anxiety Disorder (5–9)	50 (17.48%)	22 (20.18%)	0.954
Moderate Anxiety Disorder (10–14)	35 (12.24%)	21 (19.27%)	0.201
Severe Anxiety Disorder (15–21)	24 (8.39%)	31 (28.44%)	< 0.001

CORE patients were broken down by disease severity into non-hospitalized (N = 466), general floor (N = 147), and critically ill (N = 50). Across disease severity groups, higher incidence of dyspnea, fatigue, decreased exercise tolerance, and cough incidence were associated with higher disease severity. Incidence of normal or minimal depression increased as disease severity worsened. Results of anxiety questionnaires were not significantly different between disease severity groups (p > 0.05).

The demographic, disease severity, and socioeconomic profiles of CORE patients without and with unmet HRSNs are presented in Table 3A. There were no statistically significant differences in age, female sex composition, BMI, combined race and ethnicity, or comorbidities (all p > 0.05). Disease severity and vaccination status was also not significantly different between groups (p > 0.05). Patients with unmet needs had lower incidence of 5th quintile median household income (0.91% vs 5.79%, p = 0.035) and higher Medicaid use (43.64% vs 26.64%, p = 0.001) compared to patients without unmet needs.

Table 3B compares the long COVID physical symptoms and behavioral questionnaires stratified by patients without and with social needs. Only brain fog/cognitive issues were higher in patients with unmet needs (42.73% vs 32.05%, p = 0.049) compared to patients without 0 unmet needs. In the ESAS-r responses, patients with unmet needs did experience more severe symptoms compared to patients without unmet needs, with the top five severe ones being tiredness (5.70 ± 3.57 vs 4.91 ± 3.13, p = 0.002, worsened overall wellbeing (5.19 ± 2.94 vs 3.94 ± 2.96, p < 0.001), anxiety (5.14 ± 3.65 vs 3.03 ± 3.19, p < 0.001), pain (4.64 ± 3.08 vs 3.38 ± 3.03, p < 0.001), and depression (4.51 ± 3.55 vs 2.24 ± 2.94, p < 0.001). Patients with unmet needs additionally experienced worsened depression (12.05 ± 7.07 vs 7.71 ± 6.35, p < 0.001) and anxiety (9.26 ± 6.63 vs 5.28 ± 5.72, p < 0.001) as compared to patients without unmet needs. CORE patients with unmet needs had increased rates of clinically severe depression (15.60% vs 5.93%, p = 0.003) and severe anxiety disorder (28.44% vs 8.39%, p < 0.001).

This study investigated the patient characteristics and prevalence of long COVID symptoms in our CORE clinics between June 26th, 2020 and February 24th, 2023 with emphasis on the potential influence of unmet HRSNs. The major findings are: i) most CORE patients are infected during the early waves of COVID-19 and were largely unvaccinated, ii) CORE patients are of older age and more female, have higher BMI, higher prevalence of hypertension, diabetes, COPD, and asthma, lower incomes, and more unmet HRSNs compared to all COVID-19 patients in our health system, iii) COVID-19 survivors report a wide range of severe long-COVID symptoms across the physical, emotional, and cognitive health domains, iv) some COVID-related symptoms (i.e., dyspnea, fatigue, decreased exercise tolerance, and cough) show higher incidence among more severe COVID-19 patients but these symptoms were not limited to hospitalized or critically ill patients, and v) patients with unmet HRSNs have similar demographics (except lower percentage of high income bracket and higher percentage with Medicaid), but experience broadly more severe physical and psychological long-COVID symptoms compared to patients without unmet HRSNs.

Time courses

More CORE patients were infected during the early waves. These peak infection periods matched the reported SARS-CoV-2 infection spikes in New York metropolitan areas ²³. Vaccination and treatments were limited during the earlier waves of the pandemic and thus it is likely that these patients infected in earlier waves experienced more severe disease courses. Our data indicated that most CORE patients were in fact unvaccinated at the time of infection. Patients infected in later waves likely had less severe disease course and long-term outcomes as vaccines and COVID-19 treatments became more available.

Physical and neuropsychiatric symptoms

The high incidences of dyspnea, fatigue, brain fog, decreased exercise tolerance, and shortness of breath reported in this study are consistent with the literature^24,25. Goertz et al. found that fatigue, dyspnea, headache, and chest tightness were the four most common persistent symptoms 3-months after infection ²⁶. Huang et al reported that fatigue or muscle weakness was by far the most common symptom hospitalized COVID-19 patients at 6-months followed up ²⁷. Carfi et al. found fatigue, dyspnea, and joint pains to be the three most prevalent symptoms in COVID survivors about 2 months after their COVID-19 hospitalization ²⁸. These symptomologies are not surprising given many COVID-19 patients were often discharged with major medical referrals ^29,30. The incidence of dyspnea, fatigue, decreased exercise tolerance, and cough increased as disease severity worsened, in agreement with other papers ^31–33.

Additionally, CORE patients broadly showed signs of mild anxiety and mild depression. Surprisingly, the severity of anxiety and depression was inversely correlated to COVID-19 disease severity. Other studies have similarly found that after COVID-19 infection, a significant number of patients self-reported anxiety and depression^34,35. One study found that most COVID-19 survivors had mild depression, specifically using the PHQ-9 questionnaire, in agreement with our study. As anxiety and depression are known risk factors for developing PASC³⁶, it is concerning that the majority of CORE patients screened positive for clinically significant anxiety and depression.

Disease severity

Some, but not all, CORE patients showed more long-COVID symptoms and abnormal physical, emotional, and cognitive scores. More severe COVID-19, as measured by hospitalization in the general floor or ICU/IMV interventions, showed higher incidence of long COVID symptoms compared to the non-hospitalized cohort. It is striking that many non-hospitalized patients had substantial symptoms and abnormal scores. Although non-hospitalized patients who visited our CORE clinics were more likely to exhibit symptoms given the nature of their visit, these data suggested that long COVID is not limited to severely ill COVID-19 patients. Previous studies have reported individuals with mild symptoms from SARS-CoV-2 infection (i.e., not requiring hospitalization) or asymptomatic infection may also be susceptible to general and neurological PASC ^37–39.

Health Related Social Needs

CORE patients with and without unmet HRSNs had similar baseline demographics, comorbidities, or disease severity in our cohort, except patients with unmet social needs had lower proportion of 5th quintile income and more were on Medicaid as expected. However, the incidence of severe depression and anxiety was nearly tripled in patients with unmet HRSNs as compared to patients without. Patients with unmet HRSNs also experienced more severe long COVID symptoms compared to those without.

It is likely that the persistent stress associated with these unmet needs is increasingly understood as a pivotal factor, amplifying the susceptibility to and severity of long-term consequences from COVID-19. It is well known that sustained, chronic stress has several deleterious effects on normal physiology. It sets off a chain reaction within the body, sparking inflammatory responses and prompting intricate alterations in gene expression, known as epigenetic modifications ⁴⁰. These modifications, in turn, have the potential to significantly impact health outcomes, potentially worsening the long-term effects of COVID-19.

Moreover, persistent structural barriers in accessing quality health care services, particularly preventative care, places vulnerable populations at a distinct disadvantage. The higher prevalence of pre-existing health conditions among marginalized groups, often due to systemic inequalities, acts as a significant contributor to the severity of long COVID outcomes. The cumulative effect of these intersecting factors serves to magnify the disproportionate toll that COVID-19 exacts on historically marginalized populations, highlighting the urgent need for targeted interventions addressing these underlying socioeconomic disparities.

Limitations

This study has several limitations. Our findings were limited to COVID-19 survivors who came to our CORE clinics and who were more likely to have more severe COVID-19 symptoms, and thus our cohort was not representative of the general population. Multicenter and prospective studies are needed to validate these findings and achieve broader generalization. It was not possible to definitively distinguish abnormalities that were due to COVID-19, pre-existing or worsened by COVID-19 disease. SDOH data were only available for a subset of patients because these questionnaires were incorporated in 2018⁴¹ with the administration and responses being encouraged but voluntary. Long-term outcomes may have been affected by vaccination status and reinfection.

COVID-19 patients have a wide range of severe long COVID symptoms across the physical, emotional, and cognitive health domains, and these symptoms are not limited to patients who were hospitalized or critically ill. Patients with unmet social needs are more likely to experience exacerbated long COVID outcomes, furthering the widening health disparity. These findings call attention to the impacts of health disparity on socioeconomically vulnerable patients with long COVID. This pandemic has underscored the urgent need to address systemic issues and work towards equitable healthcare and support systems for all.

Author Contribution

AE – data analysis and collection, conceptualization, investigation, drafting and editing manuscript;MD – data analysis, conceptualization, investigation, drafting and editing manuscript;MG – chart review, data analysis, validation;WJ – chart review, validation;KPF – data curation, validation, editing manuscript;SC – data curation, validation, editing manuscript;TQD – conceptualization, editing manuscript, supervision

Davis, H. E. et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine 38, 101019, doi:10.1016/j.eclinm.2021.101019 (2021).
Rubin, R. As Their Numbers Grow, COVID-19 "Long Haulers" Stump Experts. JAMA 324, 1381–1383, doi:10.1001/jama.2020.17709 (2020).
Zhao, Y. M. et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine 25, 100463, doi:10.1016/j.eclinm.2020.100463 (2020).
Iosifescu, A. L., Hoogenboom, W. S., Buczek, A. J., Fleysher, R. & Duong, T. Q. New-onset and persistent neurological and psychiatric sequelae of COVID-19 compared to influenza: A retrospective cohort study in a large New York City healthcare network. Int J Methods Psychiatr Res 31, e1914, doi:10.1002/mpr.1914 (2022).
Moghimi, N. et al. The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection. Curr Neurol Neurosci Rep 21, 44, doi:10.1007/s11910-021-01130-1 (2021).
Collantes, M. E. V., Espiritu, A. I., Sy, M. C. C., Anlacan, V. M. M. & Jamora, R. D. G. Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis. Can J Neurol Sci 48, 66–76, doi:10.1017/cjn.2020.146 (2021).
Graham EL, C. J., Orban ZS, Lim PH, Szymanski AL, Taylor C, et al.. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers". Annals of Clinical and Translational Neurology, doi:10.1002/acn3.51350 (2021).
Wang, F., Kream, R. M. & Stefano, G. B. Long-Term Respiratory and Neurological Sequelae of COVID-19. Med Sci Monit 26, e928996, doi:10.12659/MSM.928996 (2020).
Bambra, C., Riordan, R., Ford, J. & Matthews, F. The COVID-19 pandemic and health inequalities. J Epidemiol Community Health 74, 964–968, doi:10.1136/jech-2020-214401 (2020).
Ambrose, A. J. H. Inequities During COVID-19. Pediatrics 146, doi:10.1542/peds.2020-1501 (2020).
Abrams, E. M. & Szefler, S. J. COVID-19 and the impact of social determinants of health. Lancet Respir Med 8, 659–661, doi:10.1016/S2213-2600(20)30234-4 (2020).
Singu, S., Acharya, A., Challagundla, K. & Byrareddy, S. N. Impact of Social Determinants of Health on the Emerging COVID-19 Pandemic in the United States. Front Public Health 8, 406, doi:10.3389/fpubh.2020.00406 (2020).
Green, H., Fernandez, R. & MacPhail, C. The social determinants of health and health outcomes among adults during the COVID-19 pandemic: A systematic review. Public Health Nurs 38, 942–952, doi:10.1111/phn.12959 (2021).
Acosta, A. M. et al. Racial and Ethnic Disparities in Rates of COVID-19-Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death in the United States From March 2020 to February 2021. JAMA Netw Open 4, e2130479, doi:10.1001/jamanetworkopen.2021.30479 (2021).
Correa-Agudelo, E. et al. Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19 Related Mortality in the U.S. medRxiv, doi:10.1101/2020.07.11.20151563 (2020).
Magesh, S. et al. Disparities in COVID-19 Outcomes by Race, Ethnicity, and Socioeconomic Status: A Systematic-Review and Meta-analysis. JAMA Netw Open 4, e2134147, doi:10.1001/jamanetworkopen.2021.34147 (2021).
Kanwal, A. et al. The Effect of Race and Socioeconomic Status on Hospitalized Patients with COVID-19 Infection. J Community Hosp Intern Med Perspect 12, 14–19, doi:10.55729/2000-9666.1035 (2022).
Saltzman, L. Y., Lesen, A. E., Henry, V., Hansel, T. C. & Bordnick, P. S. COVID-19 Mental Health Disparities. Health Secur 19, S5-s13, doi:10.1089/hs.2021.0017 (2021).
Subramanian, A. et al. Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med 28, 1706–1714, doi:10.1038/s41591-022-01909-w (2022).
Brakefield, W. S., Olusanya, O. A., White, B. & Shaban-Nejad, A. Social Determinants and Indicators of COVID-19 Among Marginalized Communities: A Scientific Review and Call to Action for Pandemic Response and Recovery. Disaster Med Public Health Prep 17, e193, doi:10.1017/dmp.2022.104 (2022).
Hoogenboom, W. S. et al. Clinical characteristics of the first and second COVID-19 waves in the Bronx, New York: A retrospective cohort study. Lancet Reg Health Am 3, 100041, doi:10.1016/j.lana.2021.100041 (2021).
Fiori, K. P. et al. Scaling-up social needs screening in practice: a retrospective, cross-sectional analysis of data from electronic health records from Bronx county, New York, USA. BMJ Open 11, e053633, doi:10.1136/bmjopen-2021-053633 (2021).
COVID-19 Data: Trends and Totals, <https://www.nyc.gov/site/doh/covid/covid-19-data-totals.page> (2023).
Eligulashvili, A. et al. COVID-19 Patients in the COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx. Diagnostics (Basel) 13, doi:10.3390/diagnostics13010119 (2022).
Yong, S. J. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond) 53, 737–754, doi:10.1080/23744235.2021.1924397 (2021).
Goertz, Y. M. J. et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res 6, doi:10.1183/23120541.00542-2020 (2020).
Huang, C. et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 397, 220–232, doi:10.1016/S0140-6736(20)32656-8 (2021).
Carfi, A., Bernabei, R., Landi, F. & Gemelli Against, C.-P.-A. C. S. G. Persistent Symptoms in Patients After Acute COVID-19. JAMA 324, 603–605, doi:10.1001/jama.2020.12603 (2020).
Musheyev, B. et al. Functional status of mechanically ventilated COVID-19 survivors at ICU and hospital discharge. J Intensive Care 9, 31, doi:10.1186/s40560-021-00542-y (2021).
Musheyev, B. et al. Characterizing non-critically ill COVID-19 survivors with and without in-hospital rehabilitation. Sci Rep 11, 21039, doi:10.1038/s41598-021-00246-1 (2021).
Taboada, M. et al. Post-COVID-19 functional status six-months after hospitalization. J Infect 82, e31-e33, doi:10.1016/j.jinf.2020.12.022 (2021).
Raman, B. et al. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine 31, 100683, doi:10.1016/j.eclinm.2020.100683 (2021).
Halpin, S. J. et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol 93, 1013–1022, doi:10.1002/jmv.26368 (2021).
Mazza, M. G. et al. Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors. Brain Behav Immun 89, 594–600, doi:10.1016/j.bbi.2020.07.037 (2020).
Taquet M, L. S., Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psychiatry 8, 1330–1140, doi:10.1016/S2215-0366(20)30462-4 (2021).
Takao, M. & Ohira, M. Neurological post-acute sequelae of SARS-CoV-2 infection. Psychiatry Clin Neurosci 77, 72–83, doi:10.1111/pcn.13481 (2023).
Townsend, L. et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS One 15, e0240784, doi:10.1371/journal.pone.0240784 (2020).
van den Borst, B. et al. Comprehensive Health Assessment 3 Months After Recovery From Acute Coronavirus Disease 2019 (COVID-19). Clin Infect Dis 73, e1089-e1098, doi:10.1093/cid/ciaa1750 (2021).
Boufidou, F. et al. SARS-CoV-2 Reinfections and Long COVID in the Post-Omicron Phase of the Pandemic. Int J Mol Sci 24, doi:10.3390/ijms241612962 (2023).
Howell, C. R. et al. Associations between cardiometabolic disease severity, social determinants of health (SDoH), and poor COVID-19 outcomes. Obesity (Silver Spring) 30, 1483–1494, doi:10.1002/oby.23440 (2022).
Heller, C. G., Parsons, A. S., Chambers, E. C., Fiori, K. P. & Rehm, C. D. Social Risks Among Primary Care Patients in a Large Urban Health System. Am J Prev Med 58, 514–525, doi:10.1016/j.amepre.2019.11.011 (2020).

No competing interests reported.

Download PDF

Journal Publication

published 02 Apr, 2024

Read the published version in Scientific Reports →

Editorial decision: Revision requested
03 Mar, 2024
Reviewers agreed at journal
28 Feb, 2024
Reviews received at journal
19 Feb, 2024
Reviewers agreed at journal
07 Feb, 2024
Reviewers invited by journal
16 Jan, 2024
Editor assigned by journal
08 Jan, 2024
Editor invited by journal
21 Dec, 2023
Submission checks completed at journal
21 Dec, 2023
First submitted to journal
19 Dec, 2023

You are reading this latest preprint version

Patients with unmet social needs are at higher risks of developing severe long COVID-19 symptoms and neuropsychiatric sequela

Status:

Journal Publication

Version 1

Abstract

Figures

INTRODUCTION

METHODS

RESULTS

DISCUSSION

Conclusions

Declarations

Author Contribution

References

Additional Declarations

Status:

Journal Publication

Version 1