Prevalence and Factors Associated with Long COVID Symptoms among U.S. Adults, 2022

Abstract:

Long COVID and its symptoms have not been examined in different subpopulations of U.S. adults. Using the 2022 BRFSS (n = 445,132), we assessed long COVID and each symptom by sociodemographic characteristics and health-related variables. Multivariable logistic regression was conducted to examine factors associated with long COVID and the individual symptoms. Prevalence differences were conducted to examine differences in long COVID by vaccination status.

Overall, more than one in five adults who ever had COVID-19 reported symptoms consistent with long COVID (21.8%). The most common symptom was tiredness or fatigue (26.2%), followed by difficulty breathing or shortness of breath (18.9%), and loss of taste or smell (17.0%). Long COVID was more common among adults under 65 years, women, American Indian or Alaska Native or other/multi race group, smokers, and people with a disability, depression, overweight or obesity compared to their respective counterparts.

The prevalence of long COVID was higher among unvaccinated adults (25.6%) than vaccinated adults (21.6%) overall, and for 20 of 32 subgroups assessed. These findings underscore the benefits of vaccination, the importance of early treatment, and the need to better inform health care resource allocation and support services for those experiencing long COVID.

Source: Nguyen KH, Bao Y, Mortazavi J, Allen JD, Chocano-Bedoya PO, Corlin L. Prevalence and Factors Associated with Long COVID Symptoms among U.S. Adults, 2022. Vaccines (Basel). 2024 Jan 18;12(1):99. doi: 10.3390/vaccines12010099. PMID: 38250912; PMCID: PMC10820629. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10820629/ (Full text)

Long Covid

Abstract:

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), refers to a constellation of persistent symptoms and health issues that continue beyond the acute phase of COVID-19. This chapter provides an overview of the pathogenesis, risk factors, manifestations, major findings, and diagnosis and treatment strategies associated with Long COVID.

Hypotheses regarding the pathogenesis of Long COVID are discussed, encompassing various factors such as persistent viral reservoirs, immune dysregulation with or without reactivation of herpesviruses (e.g., Epstein-Barr Virus and human herpesvirus), dysbiosis, autoimmunity triggered by infection, endothelial dysfunction, microvessel blood clotting, and dysfunctional brainstem and/or vagal signaling. The chapter also highlights the risk factors associated with Long COVID and its occurrence in children.

The major findings of Long COVID, including immune dysregulation, vessel and tissue damage, neurological and cognitive pathology, eye symptoms, endocrinal issues, myalgic encephalomyelitis and chronic fatigue syndrome, reproductive system involvement, respiratory and gastrointestinal symptoms, and the chronology of symptoms, are thoroughly explored.

Lastly, the chapter discusses the challenges and current approaches in the diagnosis and treatment of Long COVID, emphasizing the need for multidisciplinary care and individualized management strategies.

Source: Asiya Kamber Zaidi and Puya Dehgani-Mobaraki. Long Covid. Progress in Molecular Biology and Translational Science, Volume 202, 2024, Pages 113-125 https://www.sciencedirect.com/science/article/abs/pii/S1877117323001771

The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study

Abstract:

Long Covid-19 syndrome (LCS) manifests with a wide range of clinical symptoms, yet the factors associated with LCS remain poorly understood. The current study aimed to investigate the relationships that demographic characteristics, clinical history, laboratory indicators, and the frequency of HLA-I alleles have with the likelihood of developing LCS.

We extracted the demographic characteristics and clinical histories from the medical records of 88 LCS cases (LCS+ group) and 96 individuals without LCS (LCS group). Furthermore, we evaluated the clinical symptoms, serum levels of interleukin (IL)-6 and tumor necrosis factor-α, laboratory parameters, and the frequencies of HLA-I alleles.

Following this we used multiple logistic regression to investigate the association these variables had with LCS. Subjects in the LCS+ group were more likely to have experienced severe Covid-19 symptoms and had higher body mass index (BMI), white blood cell, lymphocyte counts, C-reactive protein (CRP), and IL-6 levels than those in the LCS group (for all: P < 0.05).

Moreover, the frequencies of the HLA-A*11, -B*14, -B*38, -B*50, and -C*07 alleles were higher in the LCS+ group (for all: P < 0.05). After adjusting for the most important variables, the likelihood of suffering from LCS was significantly associated with BMI, CRP, IL-6, the HLA-A*11, and -C*07 alleles, as well as a positive history of severe Covid-19 (for all: P < 0.05).

Our study showed that a history of severe Covid-19 during the acute phase of the disease, the HLA-A*11, and -C*07 alleles, higher BMI, as well as elevated serum CRP and IL-6 levels, were all associated with an increased likelihood of LCS.

Source: Torki, E., Hoseininasab, F., Moradi, M. et al. The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study. Clin Exp Med 24, 1 (2024). https://doi.org/10.1007/s10238-023-01256-1 https://link.springer.com/article/10.1007/s10238-023-01256-1 (Full text)

Risk factors for experiencing Long-COVID symptoms: Insights from two nationally representative surveys

Abstract:

Background Long COVID (LC) is a complex and multisystemic condition marked by a diverse range of symptoms, yet its associated risk factors remain poorly defined.

Methods Leveraging data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) and National Health Interview Survey (NHIS), both representative of the United States population, this study aimed to identify demographic characteristics associated with LC. The sample was restricted to individuals aged 18 years and older who reported a positive COVID-19 test or doctor’s diagnosis. We performed a descriptive analysis comparing characteristics between participants with and without LC. Furthermore, we developed multivariate logistic regression models on demographic covariates that would have been valid at the time of the COVID-19 infection.

Results Among the 124,313 individuals in BRFSS and 10,131 in the NHIS reporting either a positive test or doctor’s diagnosis for COVID-19 (Table), 26,783 (21.5%) in BRFSS and 1,797 (17.1%) in NHIS reported LC. In the multivariate logistic regression model, we found middle age, female gender, Hispanic ethnicity, lack of a college degree, and residence in non-metropolitan areas associated with higher risk of LC. Notably, the initial severity of acute COVID-19 was strongly associated with LC risk. In contrast, significantly lower ORs were reported for Non-Hispanic Asian and Black Americans compared to Non-Hispanic White.

Conclusions In the United States, there is marked variation in the risk of LC by demographic factors and initial infection severity. Further research is needed to understand the underlying cause of these observations.

Source: Yixuan WuMitsuaki SawanoYilun WuRishi M. ShahPamela BishopAkiko IwasakiHarlan M. Krumholz. Risk factors for experiencing Long-COVID symptoms: Insights from two nationally representative surveys.

Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort study

Abstract:

Oral nirmatrelvir/ritonavir is approved as treatment for acute COVID-19, but the effect of treatment during acute infection on risk of Long COVID is unknown. We hypothesized that nirmatrelvir treatment during acute SARS-CoV-2 infection reduces risk of developing Long COVID and rebound after treatment is associated with Long COVID. We conducted an observational cohort study within the Covid Citizen Science (CCS) study, an online cohort study with over 100 000 participants.

We included vaccinated, nonhospitalized, nonpregnant individuals who reported their first SARS-CoV-2 positive test March–August 2022. Oral nirmatrelvir/ritonavir treatment was ascertained during acute SARS-CoV-2 infection. Patient-reported Long COVID symptoms, symptom rebound and test-positivity rebound were asked on subsequent surveys at least 3 months after SARS-CoV-2 infection. A total of 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the Long COVID survey (n = 1611). Among 1611 participants, median age was 55 years and 66% were female.

At 5.4 ± 1.3 months after infection, nirmatrelvir treatment was not associated with subsequent Long COVID symptoms (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 0.80–1.64; p = 0.45). Among 666 treated who answered rebound questions, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR: 1.34; 95% CI: 0.74–2.41; p = 0.33).

Within this cohort of vaccinated, nonhospitalized individuals, oral nirmatrelvir treatment during acute SARS-CoV-2 infection and rebound after nirmatrelvir treatment were not associated with Long COVID symptoms more than 90 days after infection.

Source: Durstenfeld MSPeluso MJLin F, et al. Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort studyJ Med Virol202496:e29333. doi:10.1002/jmv.29333 https://onlinelibrary.wiley.com/doi/10.1002/jmv.29333 (Full text)

Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination

Abstract:

Background and study aims Gut infection is common during acute COVID-19, and persistent SARS-CoV-2 gut infection has been reported months after the initial infection, potentially linked to long-COVID syndrome. This study tested the incidence of persistent gut infection in patients with a history of COVID-19 undergoing endoscopic examination.

Patients and methods Endoscopic biopsies were prospectively collected from patients with previous COVID-19 infection undergoing upper or lower gastrointestinal endoscopy (UGE or LGE). Immunohistochemistry was used to detect the presence of persistent SARS-CoV-2 nucleocapsid proteins.

Results A total of 166 UGEs and 83 LGE were analyzed. No significant differences were observed between patients with positive and negative immunostaining regarding the number of previous COVID-19 infections, time since the last infection, symptoms, or vaccination status. The incidence of positive immunostaining was significantly higher in UGE biopsies than in LGE biopsies (37.34% vs. 16.87%, P =0.002). Smokers showed a significantly higher incidence of positive immunostaining in the overall cohort and UGE and LGE subgroups ( P <0.001). Diabetic patients exhibited a significantly higher incidence in the overall cohort ( P =0.002) and UGE subgroup ( P =0.022), with a similar trend observed in the LGE subgroup ( P =0.055).

Conclusions Gut mucosal tissues can act as a long-term reservoir for SARS-CoV-2, retaining viral particles for months following the primary COVID-19 infection. Smokers and individuals with diabetes may be at an increased risk of persistent viral gut infection. These findings provide insights into the dynamics of SARS-CoV-2 infection in the gut and have implications for further research.

Source: Hany M, Sheta E, Talha A, Anwar M, Selima M, Gaballah M, Zidan A, Ibrahim M, Agayby ASS, Abouelnasr AA, Samir M, Torensma B. Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination. Endosc Int Open. 2024 Jan 5;12(1):E11-E22. doi: 10.1055/a-2180-9872. PMID: 38188925; PMCID: PMC10769582. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769582/ (Full text)

 

The Multisystem Impact of Long COVID: A Comprehensive Review

Abstract:

Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods.
Methods: Recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects.
Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time.
Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.
Source: Negrut, N.; Georgios, M.; Kampioti, S.; Bourelou, M.; Kopanyi, F.; Hassan, F.D.; Asowed, A.; Taleouine, F.Z.; Ferician, A.; Marian, P. The Multisystem Impact of Long COVID: A Comprehensive Review. Preprints 2024, 2024010099. https://doi.org/10.20944/preprints202401.0099.v1 https://www.preprints.org/manuscript/202401.0099/v1 (Full text available as PDF file)

Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities.

During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

Source: Ozonoff, A., Jayavelu, N.D., Liu, S. et al. Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study. Nat Commun 15, 216 (2024). https://doi.org/10.1038/s41467-023-44090-5 https://www.nature.com/articles/s41467-023-44090-5 (Full text)

Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2

Abstract:

Objective: COVID-19 survivors can experience lingering symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) that appear in different phenotypes, and its etiology remains elusive. We assessed the relationship of endothelial dysfunction with having COVID and PASC.

Methods: Data was collected from a prospectively enrolled cohort (n=379) of COVID-negative and COVID-positive participants with and without PASC. Primary outcomes, endothelial function (measured by reactive hyperemic index [RHI]), and arterial elasticity (measured by augmentation index standardized at 75 bpm [AI]), were measured using the FDA approved EndoPAT. Patient characteristics, labs, metabolic measures, markers of inflammation, and oxidized LDL (ox-LDL) were collected at each study visit, and PASC symptoms were categorized into 3 non-exclusive phenotypes: cardiopulmonary, neurocognitive, and general. COVID-negative controls were propensity score matched to COVID-negative-infected cases using the greedy nearest neighbor method.

Results: There were 14.3% of participants who were fully recovered COVID positive and 28.5% who were COVID positive with PASC, averaging 8.64 ± 6.26 total number of symptoms. The mean RHI was similar across the cohort and having COVID or PASC was not associated with endothelial function (P=0.33). Age (P<0.0001), female sex (P<0.0001), and CRP P=0.04) were positively associated with arterial stiffness, and COVID positive PASC positive with neurological and/or cardiopulmonary phenotypes had the worst arterial elasticity (highest AI). Values for AI (P=0.002) and ox-LDL (P<0.0001) were independently and positively associated with an increased likelihood of having PASC.

Conclusion: There is evidence of an independent association between PASC, ox-LDL, and arterial stiffness with neurological and/or cardiopulmonary phenotypes having the worst arterial elasticity. Future studies should continue investigating the role of oxidative stress in the pathophysiology of PASC.

Source: Zisis SN, Durieux JC, Mouchati C, Funderburg N, Ailstock K, Chong M, Labbato D, McComsey GA. Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2. Pathog Immun. 2023 Dec 20;8(2):1-15. doi: 10.20411/pai.v8i2.634. PMID: 38156116; PMCID: PMC10753933. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10753933/ (Full text)

Analysis of post-COVID symptoms and predisposing factors for chronic post-COVID syndrome

Abstract:

Introduction: While there is sufficient information about acute COVID-19, which can cause a multisystemic and fatal disease, post-COVID syndrome and risk factors for this condition remain poorly known. We aimed to identify postCOVID symptoms and risk factors for chronic post-COVID syndrome through this study.

Materials and methods: This prospective cross-sectional study was conducted on 254 out of 384 COVID-19 patients admitted to our COVID-19 polyclinic between February and April 2021. The patients were questioned with a list of 37 symptoms at the fifth and twelfth weeks after disease onset via phone review, and their acute post-COVID (APC) and chronic post-COVID (CPC) symptoms were recorded. Data on risk factors were collected from the hospital’s medical records system. Associations between symptom count in the CPC phase and age, sex, hospitalization, RT-PCR result, specific radiological findings, comorbidities, and long-term medications were evaluated.

Result: Two hundred twenty-one patients had APC symptoms, and 138 patients had CPC symptoms. While the most common symptom was fatigue at week five, it was hair loss at week 12. Symptoms were observed significantly less in the CPC phase than in the APC phase (Z= -12.301, p= 0.00). Female sex and the presence of specific radiological findings were significantly associated with the occurrence of CPC symptoms (p= 0.03, p= 0.00, respectively). Long-term use of angiotensin-2 receptor blockers (ARBs) was correlated with a low symptom count in the CPC phase (p= 0.00).

Conclusions: Female sex and the presence of specific radiological findings were risk factors for developing CPC. Long-term use of ARBs was associated with a low chronic post-COVID symptom burden. A substantial cluster of multisystemic symptoms was observed in both phases, and this condition highlights the requirement for customized outpatient management that includes long-term follow-up and treatment of COVID-19 patients. Identifying the high-risk patients that will develop persistent symptoms can guide this management.

Source: Abalı H, Demir D, Gül Ş, Şimşek Veske N, Tural Onur S. Analysis of post-COVID symptoms and predisposing factors for chronic post-COVID syndrome. Tuberk Toraks. 2023 Dec;71(4):378-389. English. doi: 10.5578/tt.20239606. PMID: 38152008. https://pubmed.ncbi.nlm.nih.gov/38152008/ (Full text available as PDF file)