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. 2026 Jun 24;61(4):agag043. doi: 10.1093/alcalc/agag043

Evaluating acute and post-acute COVID-19 symptoms among patients with and without alcohol-related cirrhosis: implications for quality management

Dhweeja Dasarathy 1,2, Jeremy W Luk 2,2, Amy M Shui 3,4, Robert J Wong 5,6, Ramsey Cheung 7,8, Alexander Monto 9, Michael J Ostacher 10,11, Steven L Batki 12,13, Hannah R Snyder 14, Michael J Peluso 15, Derek Satre 16,17, Mandana Khalili 18,19,✉
PMCID: PMC13293245  PMID: 42341208

Abstract

Background

Patient-reported symptoms following COVID-19 exposure have been understudied in cirrhosis. This study evaluated type, severity, and persistence of symptoms along with impact on quality of life (QOL) post-SARS-CoV-2 infection in a cohort with and without alcohol-related cirrhosis.

Methods

Patients with cirrhosis receiving care in hepatology clinics at three institutions were surveyed for symptoms and liver disease QOL (LDQOL) using standardized instruments following SARS-CoV-2 infection. Acute (<30 days), post-acute (≥30 days since onset), and Long COVID (≥3 months) symptoms were compared by cirrhosis etiology and decompensated status. Associations between severe COVID-19 symptoms and LDQOL were examined using multivariable models.

Results

156 patients with prior COVID-19 exposure had a median age of 66.5 years; 18% were female; 43% had alcohol-related liver disease (ALD); and 42% decompensated cirrhosis. Among 208 surveys conducted, the median (Q1, Q3) number of symptoms reported was 6 (3, 10), with 66% reporting at least one severe/very severe symptom and 21% had Long COVID. There were no significant differences in symptoms by cirrhosis etiology or decompensation except those with ALD had higher post-acute symptoms compared to non-ALD (RR 2.17, P = .04). Moreover, the total number of severe symptoms was inversely associated with LDQOL. For each additional severe symptom reported, LDQOL decreased by 1.12 points after adjusting for age, sex, ALD, decompensated cirrhosis, and MELD-Na score (95% CI −1.70 to −0.53, P = .001).

Conclusions

Assessing severity and persistence of post-COVID-19 exposure symptoms can help clinicians address patient-reported QOL concerns, optimize cirrhosis management, and inform integrated care for ALD and AUD.

Keywords: alcohol-associated liver disease, patient-reported symptoms, cirrhosis, quality of life, patient-reported experiences

Short Summary: Among patients with cirrhosis, those with alcohol-related liver disease (ALD) reported higher post-acute COVID-19 symptoms compared to those with non-ALD. A greater number of severe symptoms were associated with lower liver disease quality of life (QOL), underscoring the need to address QOL concerns in integrated care for alcohol-related cirrhosis.

Introduction

Liver cirrhosis is a major cause of morbidity and mortality that continues to increase globally (Liu and Chen 2022). Alcohol-related liver disease (ALD) is now the most common underlying etiology of liver disease among adults being evaluated for and undergoing liver transplantation in the US (Cholankeril and Ahmed 2018, Younossi et al. 2025, Younossi et al. 2024, Patel et al. 2025). Other causes include chronic hepatitis B or C virus infection and metabolic dysfunction-associated steatotic liver disease (Schuppan and Afdhal 2008, Gines et al. 2021, Huang et al. 2023, Tapper and Parikh 2023). Aside from treating the etiology of cirrhosis and its complications, standard of care quality measures for holistic management of cirrhosis include control of cirrhosis symptoms (Tapper and Parikh 2023). Symptoms of cirrhosis may adversely impact on quality of life (QOL), a measure of well-being and function (Rajpurohit et al. 2024). Besides symptom management, helping patients improve their QOL is also an important component in the management of cirrhosis (Marchesini et al. 2001, Loria et al. 2013). Patients with cirrhosis generally report lower health-related QOL (Rabiee et al. 2021), and problematic alcohol use has been associated with worse QOL scores, especially in the domains of memory/concentration and health distress (Luk et al. 2024). Moreover, decompensation of end stage liver disease also contributes to worsening symptoms of cirrhosis (Hansen et al. 2015, Hansen et al. 2022). The adverse impact of cirrhosis on QOL is in part attributable to deterioration of physical function, mental health, and emotional well-being, as well as disease related complications such as gastrointestinal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome (Younossi et al. 2001, Kalaitzakis 2010, Rajpurohit et al. 2024).

Since 2020, most patients have experienced at least one SARS-CoV-2 infection, leading to acute COVID-19 and, in some cases, chronic, post-acute symptoms that last for months to years and with profound effects on QOL (Kanwal et al. 2019, Walia et al. 2023, Ely et al. 2024). Importantly, there is a substantial overlap in symptoms related to acute COVID-19 and decompensated cirrhosis, including fatigue, concentration and memory issues, and myalgia (Kanwal et al. 2019, Alimohamadi et al. 2020). Patient characteristics such as a history of alcohol use disorder (AUD) may also contribute to the worsening of COVID-19 symptoms (Benzano et al. 2021). However, patient-reported symptoms following COVID-19 and their implications for QOL have not been examined among patients with cirrhosis.

To address this knowledge gap, we examined endorsement of acute, post-acute, and Long COVID-19 symptoms among patients with cirrhosis. The first aim of this study included all patients and evaluated whether the total number of acute and post-acute symptoms, as well as the likelihood of experiencing any severe symptom or Long COVID, differed by etiology of cirrhosis (i.e. ALD vs. non-ALD) and complications of cirrhosis (i.e. decompensated vs. compensated). Among patients reporting at least one severe symptom, we also assessed group differences in the total number of severe symptoms. Building on this, the second aim focused specifically on patients with at least one severe COVID-19 symptom and examined whether a greater number of severe symptoms was associated with worsening of liver disease QOL.

Methods

Settings and population

Patients with cirrhosis were recruited from hepatology clinics across three sites: Palo Alto Veterans Affairs Health Care System (PAVA), San Francisco Veterans Affairs Health Care System (SFVA), and Zuckerberg San Francisco General Hospital (ZSFG). Data collection was completed in six cycles, with each lasting 6 months. During each cycle, randomly ordered lists were generated for each site to determine which patients would be invited to participate in the study. Patients could be invited to participate in more than one cycle if they were randomly selected, and a new assessment would be completed each time. Eligibility criteria included age ≥ 18 years, English- or Spanish-speaking, a clinical diagnosis of cirrhosis, and ≥ 1 hepatology clinic visit in the past 6 months. Clinical diagnosis of cirrhosis was determined based on review of hepatology clinic notes. For the current analyses, patients without a prior diagnosis of COVID-19 were excluded. This study was approved by the Institutional Review Board of the University of California, San Francisco, Stanford University, and by local review committees at PAVA, SFVA, and ZSFG.

Study procedures

Potential participants were identified using electronic medical record (EMR) and through provider direct referrals. Participants were contacted via mail, telephone, and/or in-person during clinical visits for the study. Eligible participants provided informed consent and completed clinical and questionnaire assessments.

Assessments

Demographic measures

Demographic characteristics included participants’ age, sex at birth, and self-reported race/ethnicity.

COVID-19 history and symptoms

Patients completed a questionnaire regarding their medical history, including a detailed assessment of SARS-CoV-2 infection history, and EMR data was used to confirm infection if available. COVID-19 symptoms were assessed using a structured questionnaire (Peluso et al. 2022) that included date, type, and severity of symptoms (Supplemental 1). For each symptom, patients were asked when they first began experiencing the symptom, whether it was present in the first three days of illness, and whether they were still experiencing the symptom. Patients were asked to rate the severity of their symptoms ranging from 1 (not at all) to 5 (very much) on a Likert response scale. Acute symptoms were defined as occurring at less than 30 days since onset and post-acute at 30 or more days since onset.

Long COVID

Patients were considered to have Long COVID if they reported the presence of symptoms attributable to COVID-19 for at least 3 months following a preceding SARS-CoV-2 infection; the case definition used was broadly consistent with the consensus definition from the National Academies of Sciences, Engineering, and Medicine (Ely et al. 2024).

Problematic drinking

The Alcohol Use Disorders Identification Test (AUDIT) was developed by the World Health Organization for screening and assessing hazardous alcohol use in primary care settings. In general, a score of 8 or above is a well-established clinical threshold that indicates problematic alcohol use and increased risk of experiencing alcohol-related harms (Conigrave et al. 1995).

Liver disease etiology and severity

Liver disease etiology (ALD vs. non-ALD) was determined from EMR chart review of hepatology clinic notes and laboratory data using standardized procedures. Decompensated cirrhosis (vs. none) was defined by presence or history of ascites, variceal bleeding, encephalopathy, or Child-Pugh Class B or C (Martin et al. 2014). The Model for End-Stage Liver Disease-Sodium (MELD-Na) score was calculated based on laboratory measures obtained within the past 6 months for each assessment completed (Kim et al. 2008).

Quality of life assessment

The Short Form of Liver Disease Quality of Life Instrument (SF-LDQOL) is a validated assessment used to measure health related QOL in patients with liver disease (Gralnek et al. 2000). The assessment includes 14 domains (e.g. confusion, difficulties with concentration, difficulty with sexual function) ranging from 1 (all of the time) to 5 (none of the time) on a Likert scale.

Data analyses

Descriptive statistics on demographic and clinical characteristics were obtained for the study sample of 156 patients. Of these patients, 117 completed one assessment cycle, 27 completed two assessment cycles, 11 completed 3 assessment cycles, and 1 completed 4 assessment cycles with each assessment cycle occurring at least 6 months apart, yielding a total of 208 survey records for inferential statistical analyses. Whenever possible, repeated-measures analyses were conducted to account for the correlation within patients with multiple survey records. As specified below, simplified models were utilized for the analyses of post-acute symptoms due to fewer number of survey records.

Addressing the first study aim, group differences (i.e. ALD vs. non-ALD and decompensated vs. compensated) in the total number of acute and post-acute COVID-19 symptoms were tested using repeated-measures negative binomial models, which accounted for over-dispersion of count outcomes. For binary outcomes including any acute or post-acute severe symptoms (defined as 4 [severe] or 5 [very severe] on the Likert scale of severity) and Long COVID, repeated-measures log-binomial regressions were used. As Long COVID was a common outcome (>10%), relative risk (RR) was estimated rather than odds ratios. Among patients reporting at least one severe acute symptom, group differences in the number of acute symptoms were tested using repeated-measures negative binomial models. Eight patients with <30 days from SARS-CoV-2 infection to survey date were excluded from the post-acute symptoms analyses. As there were only 24 patients (30 survey records) with at least one severe post-acute COVID-19 symptom, the analyses involving total number of severe post-acute symptoms were simplified to Wilcoxon rank-sum tests.

Addressing the second study aim which focused specifically on patients with at least one severe COVID-19 symptom, the associations between the number of overall/acute severe COVID-19 symptoms and liver disease QOL were evaluated using linear mixed effects models with a random intercept, which accounted for the correlation within patients with multiple survey records. Demographic and clinical characteristics of the group of participants without sufficient time from SARS-CoV-2 infection to survey date to determine their Long COVID status were compared to the group of participants with at least 3 months of follow-up using chi-square and Wilcoxon rank-sum tests. As only 24 participants reported at least one severe post-acute COVID symptom, the analysis involving total number of post-acute severe symptoms was simplified to unadjusted ordinary linear regression (for QOL vs. number of symptoms) on the 30 survey records. For these analyses with liver disease QOL being the outcome, univariable models were first conducted. If the univariable models had significant associations, we performed multivariable models controlling for age, sex, ALD, decompensated cirrhosis, and MELD-Na score (≤5% missing data for each, with complete case analysis presented). To rule out alternative explanations, two sensitivity analyses were performed for the multivariable liver disease QOL (vs. number of severe symptoms) model. In the first sensitivity analysis, we removed MELD-Na score as a covariate as severe SARS-CoV-2 infections can alter renal/liver functions and impact MELD-Na scores. In the second sensitivity analysis, we additionally controlled for mean number of days from symptom onset to survey date for any symptoms. Hypothesis tests were two-sided and the significance threshold was set to 0.05. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA).

Results

Participant demographic and clinical characteristics

The study sample included 156 patients with cirrhosis enrolled between January of 2022 and December of 2024. Patients were enrolled from three different sites including PAVA (n = 71), SFVA (n = 30), and ZSFG (n = 55). The median (Q1, Q3) patient age was 66.5 (58.7, 72.0), 82% were male, 38.1% Latino, 36.1% White, 10.3% Black, 7.1% Asian, and 8.4% other races (Table 1). At the patient level, 12.8% of the study sample had problematic drinking (AUDIT ≥8), 42.9% had ALD, and 41.6% had decompensated cirrhosis. At the survey record level, 10.1% of the assessment records had problematic drinking, 39.4% had ALD, and 39.4% had decompensated cirrhosis.

Table 1.

Demographic and clinical characteristics of the study sample.

Continuous variables N Median Q1, Q3
Age (years) 156 66.5 58.7, 72.0
SF-liver disease QOL score 156 73.4 60.6, 86.8
MELD-Na score 149 9.0 8.0, 14.0
Total number of severe COVID symptoms (Likert 4 or 5) 92a 6.0 3.0, 11.5
Categorical variables N Frequency Percentage
Male 156 128 82.1%
Race/ethnicity 155
 White/Caucasian 56 36.1%
 Black/African American 16 10.3%
 Latino 59 38.1%
 Asian/Pacific Islander 11 7.1%
 Other 13 8.4%
Site 156
 Palo Alto Veterans Affairs Health Care System 71 45.5%
 San Francisco Veterans Affairs Health Care System 30 19.2%
 Zuckerberg San Francisco General Hospital 55 35.3%
AUDIT score 156
 High risk (8+) 20 12.8%
Liver etiology 156
 Alcohol (yes/no) 67 42.9%
 Hepatitis B (yes/no) 8 5.1%
 Hepatitis C (yes/no) 64 41.0%
 MASLD/MASH (yes/no) 35 22.4%
 Other (yes/no) 13 8.3%
Decompensated cirrhosis 149
 Current 30 20.1%
 Prior 32 21.5%
 None 87 58.4%
Any severe COVID Symptoms 135b 92 68.1%
Long COVID 116 24 20.7%
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Q1 = 1st quartile, Q3 = 3rd quartile. MASLD = Metabolic Dysfunction-Associated Steatotic Liver Disease. MASH = Metabolic Dysfunction-Associated Steatohepatitis.

aSubgroup with at least one severe COVID-19 symptom.

bSubgroup with at least one COVID-19 symptom.

The median (Q1, Q3) number of days from most recent SARS-CoV-2 infection date of diagnosis was 433 (187, 756) for patients with at least one current symptom. Overall, the most common symptoms experienced by patients were fatigue, cough, and fever. The most common acute symptoms were fever, fatigue, and cough (see Fig. 1 for percentages by groups), and the most common post-acute symptoms were trouble with taste, sleeping, and fatigue (see Fig. 2 for percentages by groups).

Figure 1.

For image description, please refer to the figure legend and surrounding text.

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Top 15 acute COVID-19 symptoms are presented by group: patients with decompensated cirrhosis (Panel a), patients with compensated cirrhosis (Panel b), patients with ALD (Panel c), and patients without ALD (Panel d).

Figure 2.

For image description, please refer to the figure legend and surrounding text.

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Top 15 post-acute COVID-19 symptoms are presented by group: patients with decompensated cirrhosis (Panel a), patients with compensated cirrhosis (Panel b), patients with ALD (Panel c), and patients without ALD (Panel d).

Total number of symptoms

The median (Q1, Q3) total number of COVID-19 symptoms patients reported was 6 (3, 10), with 3 (0, 8) acute symptoms and 0 (0, 0) post-acute symptoms. Table 2 summarizes the acute and post-acute symptoms (total number, any severe symptoms, number of severe symptoms) by ALD and decompensated cirrhosis status. On negative binomial regression models, there were no statistically significant differences in total number of symptoms across groups.

Table 2.

Comparisons of COVID-19 symptoms by groups.

Overall ALD Non-ALD Decompensated Compensated
P P
Acute symptoms
Total number, mean (SD) 4.7 (5.7) 4.8 (6.0) 4.7 (5.6) .90 5.2 (6.9) 4.5 (4.9) .41
Any severe symptom, n (%)
No
Yes		 57 (38%)
93 (62%)		 20 (33%)
40 (67%)		 37 (41%)
53 (59%)		 .35 18 (34%)
35 (66%)		 33 (37%)
56 (63%)		 .75
Number of severe symptoms, mean (SD) 7.0 (5.8) 6.3 (5.7) 7.4 (5.9) .38 7.8 (6.5) 6.2 (5.3) .16
Post-acute symptoms
Total number, mean (SD) 0.6 (1.5) 0.7 (1.8) 0.5 (1.3) .20 0.7 (2.0) 0.5 (1.3) .31
Any severe symptom, n (%)
No
Yes		 100 (77%)
30 (23%)		 35 (69%)
16 (31%)		 65 (82%)
14 (18%)		 .04 32 (74%)
11 (26%)		 62 (78%)
18 (22%)		 .46
Number of severe symptoms, median (Q1, Q3)a 1.5 (1.0, 3.0) 2.0 (1.0, 3.0) 1.0 (1.0, 3.0) .37 2.0 (1.0, 5.0) 1.0 (1.0, 2.0) .21
Long COVID
Met criteria, n (%)
No
Yes		 126 (81%)
30 (19%)		 48 (77%)
14 (23%)		 78 (83%)
16 (17%)		 .32 42 (81%)
10 (19%)		 75 (80%)
19 (20%)		 .95
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Note. For total number of acute or post-acute symptoms, group comparisons were evaluated using repeated-measures negative binomial models. For any severe symptoms (both acute and post-acute) and long COVID, group comparisons were evaluated using repeated-measures log-binomial models. For number of severe acute symptoms among those with at least one, group comparisons were evaluated using repeated-measures negative binomial models.

aFor number of severe symptoms in post-acute phase, group comparisons were evaluated using Wilcoxon rank-sum tests.

Long COVID

Of the 116 patients with any symptoms and at least 3 months from SARS-CoV-2 infection to survey date (14 patients did not report any symptoms, 26 had 3 months from SARS-CoV-2 infection to survey date), 21% (n = 24) met the case definition for Long COVID. Of the demographic and clinical characteristics assessed, only age differed significantly when comparing the group of participants without sufficient follow-up time to determine their Long COVID status to the group of participants with at least 3 months of follow-up [median (Q1, Q3) 63.5 (58, 70) vs. 67 (61, 72) years, respectively, P = .0495]. The prevalence of Long COVID was 23% among those with ALD and 17% among those with non-ALD and 19% among those with decompensated cirrhosis versus 20% among those with compensated cirrhosis. The most reported Long COVID symptoms were trouble with sleeping, taste, and smell. Long COVID was not significantly associated with liver disease QOL (estimate −2.54, 95% CI −8.75 to 3.66, P = .41).

Severity of symptoms

We further examined patients who reported having any severe or very severe symptoms, defined as a rating of 4 or 5 on the 5-point Likert Scale. Of 174 observations with symptom and rating data available, 66% (n = 115) endorsed having at least 1 severe COVID symptom, with 62% (93/150) in acute and 23% (30/130) in post-acute phase of infection. The proportion of surveys showing at least one severe symptom by cirrhosis etiology and decompensation status were as follows: 70% in ALD [acute 67% (40/60); post-acute 31% (16/51)] versus 63% in non-ALD [acute 59% (53/90); post-acute 18% (14/79)] and 66% decompensated cirrhosis [acute 66% (35/53); post-acute 26% (11/43)] versus 69% compensated [acute 63% (56/89); post-acute 23% (18/80)].

Overall, the risk of any severe symptom did not differ significantly between groups (ALD vs. non-ALD: RR 1.11, 95% CI 0.88–1.40, P = .37 and decompensated vs. compensated cirrhosis: RR 0.94, 95% CI 0.75–1.18, P = .61), but the risk of any post-acute severe symptom was significantly higher in ALD compared to non-ALD (RR 2.17, 95% CI 1.05–4.48, P = .04).

Associations between symptom severity and liver disease quality of life

The median (Q1, Q3) overall liver disease QOL score for those with any severe symptom was 74.4 (61.0, 85.9) [acute phase: 73.4 (61.0, 84.9); post-acute: 74.4 (61.4, 84.5)] and for those without any severe symptoms was 78.8 (61.9, 91.4) [acute phase: 83.2 (65.4, 91.4); post-acute: 80.9 (63.9, 88.8)]. Overall, those with severe symptoms had a 4 points lower liver disease QOL than those with non-severe symptoms, but this association was not statistically significant (estimate −3.95, 95% CI −9.03 to 1.14, P = .12) and was also not significant for acute or post-acute symptoms.

Of the survey records reporting at least one severe symptom (n = 115; acute n = 93, post-acute n = 30), we examined the total number of severe symptoms reported between (i) ALD versus non-ALD, and (ii) decompensated versus compensated cirrhosis. The number of severe symptoms overall did not significantly differ between groups as well as among those with acute and post-acute phase or those with or without Long COVID (Table 2).

Linear mixed effects models with a random intercept were run to determine if liver disease QOL decreased with increasing number of severe COVID-19 symptoms among those with at least one severe symptom (Table 3). For overall severe symptoms, our primary analyses showed that each additional severe symptom was associated with 1.30 point decrease (95% CI -1.38, −0.78, P < .001) in liver disease QOL before adjusting for covariates, and was associated with 1.12 point decrease (95% CI −1.70, −0.53, P = .001) after adjusting for covariates. For acute severe symptoms, our primary analyses showed that each additional severe symptom was associated with 1.15 point decrease (95% CI −1.77, −0.54, P = .001) in liver disease QOL before adjusting for covariates, and was associated with 0.93 point decrease (95% CI −1.61, −0.25, P = .01) after adjusting for covariates. For both overall and acute symptoms, these associations remained significant in sensitivity analyses. In the subgroup with at least one severe post-acute symptom (n = 24 participants with 30 survey records), there was no significant association between severity of symptoms and liver disease QOL.

Table 3.

Unadjusted and adjusted associations between number of severe COVID-19 symptoms and liver disease QOL.

Liver disease QOL
Primary analyses Sensitivity analyses
Univariable Multivariable Excluded MELD-Na as a covariate Controlled for days from symptom onset to survey
Total number of severe symptoms b (95% CI) p b (95% CI) p b (95% CI) p b (95% CI) p
1. Overall severe symptoms −1.30 (−1.38, −0.78) <0.001 −1.12 (−1.70, −0.53) 0.001 −1.14 (−1.72, −0.57) <0.001 −0.94 (−1.58, −0.30) 0.007
2. Acute severe symptoms −1.15 (−1.77, −0.54) 0.001 −0.93 (−1.61, −0.25) 0.01 −0.94 (−1.62, −0.26) 0.01 −0.91 (−1.62, −0.20) 0.02
3. Post-acute severe symptoms −1.05 (−4.28, 2.17) 0.51 — — — — — —
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Note. Analyses were conducted among patients with any severe/very severe COVID-19 symptoms. For overall and acute symptoms, linear mixed effects models with a random intercept were used, and the adjusted models controlled for age, sex, ALD, decompensated cirrhosis, and MELD-Na score. For post-acute symptoms, ordinary linear regression was used.

Discussion

We found that patients with cirrhosis had a similar number of COVID-19 symptoms and exhibited a similar symptom profile during the acute phase of infection as observed in the general population (Baj et al. 2020). However, patients with cirrhosis report an average of nearly 5 symptoms with over 60% experiencing at least one severe symptom in the acute phase of infection and one in five patients met criteria for Long COVID. We also identified a relationship between COVID-19 symptoms and patient-reported QOL that was independent of cirrhosis etiology or decompensation status.

Prior studies suggest some overlap between symptoms of cirrhosis and COVID-19 (Kanwal et al. 2019, Alimohamadi et al. 2020). Patients with cirrhosis, especially those with decompensated disease, are more susceptible to severe COVID due to a relatively immunosuppressed state (Keskin et al. 2022, Shi et al. 2023, Menezes et al. 2025, Sharma et al. 2025). In addition, AUD may also be associated with increased risk of SARS-CoV-2 infection and a more complicated course of COVID-19 (Moon et al. 2021, Bailey et al. 2022). We had therefore hypothesized that those with ALD cirrhosis etiology or those with decompensated disease may be more likely to have a worse symptom profile in our cohort. Although our study did not find significant differences in the number of symptoms by cirrhosis etiology or severity nor a relationship between symptom severity and cirrhosis decompensation per se, the risk of severe post-acute symptoms tended to be higher among those with ALD compared to those with non-ALD cirrhosis. This suggests that while the management of COVID-19 symptoms may not specifically need to be modified for individuals with cirrhosis subgroups, screening for symptoms is important, especially among those with ALD etiology.

Prior studies in the general population have shown an increased symptom burden and decreased QOL with a history of COVID-19 (Di Fusco et al. 2023, Xu and Brodszky 2024). QOL is an important patient-reported outcome in both cirrhosis (Tapper et al. 2018) and AUD (Hagman et al. 2022, Luk et al. 2022) management. In our study of patients with cirrhosis linked to hepatology care, those with at least one severe COVID symptom reported lower liver disease QOL as the number of severe symptoms increased (Luk et al. 2024). The current findings are unique in showing that the inverse association between COVID-19 symptoms and burden on QOL was limited to severe symptoms only. This highlights the critical importance of assessment of symptom severity in the management of patients with cirrhosis, especially following COVID exposure, as part of comprehensive hepatology care.

Strengths of our study included post COVID exposure comprehensive symptom assessment across all stages in a diverse sample of patients from three different clinical sites and within the context of hepatology care. The study also has several limitations. First, the assessment of COVID-19 symptoms was based on self-report, which may be vulnerable to recall bias and response bias. Second, most participants provided data at one time point only and so the cross-sectional findings are limited in drawing causal inferences. Further, the study included patients with hepatology clinic visits in the past 6 months, possibly excluding those with the most severe COVID-19 episodes or who died and may therefore limit the generalizability of the findings. Lastly, the lack of association between COVID-19 symptom severity and decompensated liver disease may be related to the known higher rate of mortality among those with liver decompensation, thereby limiting our assessment to those recovering from infection.

In summary, the current study utilized a diverse sample of patients with comprehensive assessment and showed that assessing severity and chronicity of post-COVID-19 exposure symptoms can help clinicians address patient-reported QOL concerns, optimize cirrhosis management, and inform integrated care for ALD and AUD.

Supplementary Material

Supplements_agag043
supplements_agag043.docx (17.1KB, docx)

Acknowledgements

None.

Contributor Information

Dhweeja Dasarathy, Department of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, United States.

Jeremy W Luk, Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, 10 Center Drive, Room 1-5330, Bethesda, MD 20892, United States.

Amy M Shui, Department of Epidemiology and Biostatistics, University of California, 550 16th Street, #2536, San Francisco, CA 94158, United States; University of California San Francisco Liver Center, 513 Parnassus Avenue, San Francisco, CA 94143, United States.

Robert J Wong, Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA 94304, United States; Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, United States.

Ramsey Cheung, Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA 94304, United States; Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, United States.

Alexander Monto, Division of Gastroenterology and Hepatology, Veterans Affairs San Francisco Health Care System, 4150 Clement St., San Francisco, CA 94121, United States.

Michael J Ostacher, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3801 Miranda Avenue, Palo Alto, CA 94304,  United States; Department of Psychiatry, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, United States.

Steven L Batki, Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, 675 18th Street, San Francisco, CA 94107, United States; Mental Health Service, Veterans Affairs San Francisco Health Care System, 4150 Clement Street, San Francisco, CA 94121, United States.

Hannah R Snyder, Department of Family and Community Medicine, University of California, 2540 23rd Street, #5601, San Francisco, CA 94110, United States.

Michael J Peluso, Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, 2540 23rd Street, #4807, San Francisco, CA 94110, United States.

Derek Satre, Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, 675 18th Street, San Francisco, CA 94107, United States; Kaiser Permanente Northern California, Division of Research, 4480 Hacienda Drive, Pleasanton, CA 94588, United States.

Mandana Khalili, Division of Gastroenterology and Hepatology, Zuckerberg San Francisco General, 1001 Potrero Avenue, San Francisco, CA 94110, United States; Department of Medicine, University of California, 1001 Potrero Avenue, San Francisco, CA 94110, United States.

Conflicts of interest

M.K. is a recipient of research grants (to her institution) from Gilead Sciences and Intercept Pharmaceuticals, and she has served as a consultant for Gilead Sciences, GSK Pharmaceuticals, and Resolution Therapeutics. R.W. has received research grants (to his institution) from Gilead Sciences, Exact Sciences, Madrigal Pharmaceuticals, Thera Technologies, and Durect Corporation, and has served as a consultant (without honorarium) to Gilead Sciences, Salix, and Mallinckrodt Pharmaceuticals. MJP has received consulting fees from Gilead Sciences, AstraZeneca, BioVie, Apellis Pharmaceuticals, and BioNTech, travel support from Invivyd, and research support from Aerium Therapeutics and Shionogi, outside the submitted work. Other authors have no conflicts of interest to report.

Funding

This study was supported by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) R01AA029312 (M.K. and D.D.S.), K24AA022523 (M.K.), K24AA025703 (D.D.S.), and P30DK026743, and in part by the Intramural Research Program of the National Institutes of Health (J.W.L.). The contributions of the NIH author (J.W.L.) were made as part of his official duties as a NIH federal employee, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the US Department of Health and Human Services.

Data availability

This study has submitted and shared data with the National Institute on Alcohol Abuse and Alcoholism Data Archive (NIAAADA), a data repository housed within the National Institute of Mental Health (NIMH) Data Archive (NDA). Access criteria will follow NIAAADA guidelines.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplements_agag043
supplements_agag043.docx (17.1KB, docx)

Data Availability Statement

This study has submitted and shared data with the National Institute on Alcohol Abuse and Alcoholism Data Archive (NIAAADA), a data repository housed within the National Institute of Mental Health (NIMH) Data Archive (NDA). Access criteria will follow NIAAADA guidelines.

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