Integrating patient-reported physical, mental, and social impacts to classify long COVID experiences

Abstract:

Long COVID was originally identified through patient-reported experiences of prolonged symptoms. Many studies have begun to describe long COVID; however, this work typically focuses on medical records, instead of patient experiences, and lacks a comprehensive view of physical, mental, and social impacts.

As part of our larger My COVID Diary (MCD) study, we captured patient experiences using a prospective and longitudinal patient-reported outcomes survey (PROMIS-10) and free-text narrative submissions. From this study population, we selected individuals who were still engaged in the MCD study and reporting poor health (PROMIS-10 scores < 3) at 6 months (n = 634). We used their PROMIS-10 and narrative data to describe and classify their long COVID experiences.

Using Latent Class Analysis of the PROMIS-10 data, we identified four classifications of long COVID experiences: a few lingering issues (n = 107), significant physical symptoms (n = 113), ongoing mental and cognitive struggles (n = 235), and numerous compounding challenges (n = 179); each classification included a mix of physical, mental, and social health struggles with varying levels of impairment. The classifications were reinforced and further explained by patient narratives. These results provide a new understanding of the varying ways that long COVID presents to help identify and care for patients.

Source: Vartanian K, Fish D, Kenton N, Gronowski B, Wright B, Robicsek A. Integrating patient-reported physical, mental, and social impacts to classify long COVID experiences. Sci Rep. 2023 Sep 28;13(1):16288. doi: 10.1038/s41598-023-43615-8. PMID: 37770554; PMCID: PMC10539528. https://www.nature.com/articles/s41598-023-43615-8 (Full text)

15-month post-COVID syndrome in outpatients: Attributes, risk factors, outcomes, and vaccination status – longitudinal, observational, case-control study

Abstract:

Background: While the short-term symptoms of post-COVID syndromes (PCS) are well-known, the long-term clinical characteristics, risk factors and outcomes of PCS remain unclear. Moreover, there is ongoing discussion about the effectiveness of post-infection vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) to aid in PCS recovery.

Methods: In this longitudinal and observational case-control study we aimed at identifying long-term PCS courses and evaluating the effects of post-infection vaccinations on PCS recovery. Individuals with initial mild COVID-19 were followed for a period of 15 months after primary infection. We assessed PCS outcomes, distinct symptom clusters (SC), and SARS-CoV-2 immunoglobulin G (IgG) levels in patients who received SARS-CoV-2 vaccination, as well as those who did not. To identify potential associating factors with PCS, we used binomial regression models and reported the results as odds ratios (OR) with 95% confidence intervals (95%CI).

Results: Out of 958 patients, follow-up data at 15 month after infection was obtained for 222 (23.2%) outpatients. Of those individuals, 36.5% (81/222) and 31.1% (69/222) were identified to have PCS at month 10 and 15, respectively. Fatigue and dyspnea (SC2) rather than anosmia and ageusia (SC1) constituted PCS at month 15. SARS-CoV-2 IgG levels were equally distributed over time among age groups, sex, and absence/presence of PCS. Of the 222 patients, 77.0% (171/222) were vaccinated between 10- and 15-months post-infection, but vaccination did not affect PCS recovery at month 15. 26.3% of unvaccinated and 25.8% of vaccinated outpatients improved from PCS (p= .9646). Baseline headache (SC4) and diarrhoea (SC5) were risk factors for PCS at months 10 and 15 (SC4: OR 1.85 (95%CI 1.04-3.26), p=.0390; SC5: OR 3.27(95%CI 1.54-6.64), p=.0009).

Conclusion: Based on the specific symptoms of PCS our findings show a shift in the pattern of recovery. We found no effect of SARS-CoV-2 vaccination on PCS recovery and recommend further studies to identify predicting biomarkers and targeted PCS therapeutics.

Source: Augustin M, Stecher M, Wüstenberg H, Di Cristanziano V, Sandaradura de Silva U, Picard LK, Pracht E, Rauschning D, Gruell H, Klein F, Wenisch C, Hallek M, Schommers P, Lehmann C. 15-month post-COVID syndrome in outpatients: Attributes, risk factors, outcomes, and vaccination status – longitudinal, observational, case-control study. Front Immunol. 2023 Sep 12;14:1226622. doi: 10.3389/fimmu.2023.1226622. PMID: 37781408; PMCID: PMC10540070. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540070/ (Full text)

Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome

Abstract:

Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms.

Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021-May 2022 (median 243 days post-COVID-19 infection). DNA virus-related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls.

Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p < 0.001), significantly less cumulative DNA virus-related IgM positivity, significantly lower levels of plasma IgG subfractions 2 and 4, and significantly lower quantitative cytomegalovirus IgG and IgM and EBV IgM titers. These results indicate that anti-SARS-CoV-2 vaccination may interrupt viral cross-talk in patients with long-COVID syndrome (ClinicalTrials.gov Identifier: NCT05398952).

Source: Gyöngyösi M, Lukovic D, Mester-Tonczar J, Zlabinger K, Einzinger P, Spannbauer A, Schweiger V, Schefberger K, Samaha E, Bergler-Klein J, Riesenhuber M, Nitsche C, Hengstenberg C, Mucher P, Haslacher H, Breuer M, Strassl R, Puchhammer-Stöckl E, Loewe C, Beitzke D, Hasimbegovic E, Zelniker TA. Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome. NPJ Vaccines. 2023 Sep 29;8(1):145. doi: 10.1038/s41541-023-00739-2. PMID: 37773184; PMCID: PMC10541897. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541897/ (Full text)

The Long Road of Long COVID: Specific Considerations for the Allergist and Immunologist

Abstract:

Long COVID (coronavirus disease 2019) syndrome, also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a new disorder that can develop after an acute infection with the SARS-CoV-2 virus. The condition is characterized by multiorgan system involvement with a wide range of symptoms that can vary in severity from mild to debilitating.

Some of the common symptoms associated with long COVID syndrome include cardiovascular issues such as heart palpitations and chest pain; thrombotic events (eg, blood clotting disorders); metabolic problems (eg, type 2 diabetes); dysautonomia; paroxysmal orthostatic tachycardia syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; reactivation of the Epstein-Barr virus; the presence of autoantibodies; chronic spontaneous urticaria (hives); and connective tissue diseases.

Whereas long COVID syndrome can affect individuals from various backgrounds, certain populations may be at higher risk such as individuals of Hispanic and Latino heritage, as well as those with low socioeconomic status, although approximately one-third of affected patients have no known risk factors or preexisting conditions.

Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. Whereas vaccination has been the most significant intervention able to decrease the severity of acute SARS-Cov2 infection and curtail deaths, limited data are available related to its modulating effect on long COVID necessitating the need for further investigation. Furthermore, several inflammatory pathways have been proposed for the pathogenesis of long COVID that are the targets for ongoing clinical studies evaluating novel pharmacological agents.

The purpose of the present report is to review the many factors associated with long COVID with a focus on those aspects that have relevance to the allergist-immunologist.

Source: Bellanti JA, Novak P, Faitelson Y, Bernstein JA, Castells MC. The Long Road of Long COVID: Specific Considerations for the Allergist and Immunologist. J Allergy Clin Immunol Pract. 2023 Sep 27:S2213-2198(23)01045-0. doi: 10.1016/j.jaip.2023.09.014. Epub ahead of print. PMID: 37774781. https://www.sciencedirect.com/science/article/abs/pii/S2213219823010450

Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts

Abstract:

Background: The respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a multi-organ disorder, with long-term effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease (COVID).

Aim: To examine the current knowledge and outcomes of long-term neurological and gastrointestinal (GI) symptoms in adult cohorts, including United States minority populations.

Methods: PubMed and Google Scholar were searched using relevant terms, and data from five studies were analyzed, comprising 27383 patients with persistent neurological and GI sequelae.

Results: The main symptoms included anxiety, depression, dysphagia, headache, vomiting, nausea, gastroesophageal reflux, fatigue, and abdominal pain. Patients with comorbidities and metabolic syndromes were at higher risk for long COVID. While most patients were European Americans, there was a need for further study on African Americans.

Conclusion: The underlying causes of these symptoms remain unclear, warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.

Source: Sherif ZA, Deverapalli M, Challa SR, Martirosyan Z, Whitesell P, Pizuorno AM, Naqvi Z, Tulloch IK, Oskrochi G, Brim H, Ashktorab H. Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts. World J Methodol. 2023 Sep 20;13(4):323-336. doi: 10.5662/wjm.v13.i4.323. PMID: 37771866; PMCID: PMC10523249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523249/ (Full text)

Post-COVID-19 cholangiopathy: Systematic review

Abstract:

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on global health, primarily characterized by severe respiratory illness. However, emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis (SC), referred to as post-COVID-19 cholangiopathy.

Aim: To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy.

Methods: Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies, which were combined using Boolean operators. Searches were conducted on electronic databases including Scopus, Web of Science, and MEDLINE (PubMed). Studies published in English, Spanish, or Portuguese were included, with no restrictions on the publication date. Additionally, the reference lists of retrieved studies were manually searched. Simple descriptive analyses were used to summarize the results. Then the data were extracted and assessed based on Reference Citation Analysis (https://www.referencecitationanalysis.com/).

Results: The initial search yielded a total of 192 articles. After screening, 85 articles were excluded due to duplication, leaving 107 articles for further review. Of these, 63 full-length articles met the inclusion criteria and were included in the analyses. Most of the patients were male and exhibited elevated liver function tests (93.8%). Magnetic resonance imaging revealed duct thickening with contrast enhancement (47.7%), as well as beading of the intrahepatic ducts (45.7%) with peribiliary contrast enhancement on diffusion (28.7%). Liver biopsy results confirmed SC in most cases (74.4%). Sixteen patients underwent liver transplantation, with three experiencing successful outcomes.

Conclusion: Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years, particularly considering long COVID syndromes. Although liver transplantation has been proposed as a potential treatment option, more research is necessary to establish its efficacy and explore other potential treatments.

Source: Rasheed MA, Ballotin VR, Bigarella LG, Soldera J. Post-COVID-19 cholangiopathy: Systematic review. World J Methodol. 2023 Sep 20;13(4):296-322. doi: 10.5662/wjm.v13.i4.296. PMID: 37771872; PMCID: PMC10523251. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523251/ (Full text)

A brief overview of SARS-CoV-2 infection and its management strategies: a recent update

Abstract:

The COVID-19 pandemic has become a global health crisis, inflicting substantial morbidity and mortality worldwide. A diverse range of symptoms, including fever, cough, dyspnea, and fatigue, characterizes COVID-19. A cytokine surge can exacerbate the disease’s severity. This phenomenon involves an increased immune response, marked by the excessive release of inflammatory cytokines like IL-6, IL-8, TNF-α, and IFNγ, leading to tissue damage and organ dysfunction.

Efforts to reduce the cytokine surge and its associated complications have garnered significant attention. Standardized management protocols have incorporated treatment strategies, with corticosteroids, chloroquine, and intravenous immunoglobulin taking the forefront. The recent therapeutic intervention has also assisted in novel strategies like repurposing existing medications and the utilization of in vitro drug screening methods to choose effective molecules against viral infections.

Beyond acute management, the significance of comprehensive post-COVID-19 management strategies, like remedial measures including nutritional guidance, multidisciplinary care, and follow-up, has become increasingly evident. As the understanding of COVID-19 pathogenesis deepens, it is becoming increasingly evident that a tailored approach to therapy is imperative.

This review focuses on effective treatment measures aimed at mitigating COVID-19 severity and highlights the significance of comprehensive COVID-19 management strategies that show promise in the battle against COVID-19.

Source: Das A, Pathak S, Premkumar M, Sarpparajan CV, Balaji ER, Duttaroy AK, Banerjee A. A brief overview of SARS-CoV-2 infection and its management strategies: a recent update. Mol Cell Biochem. 2023 Sep 24. doi: 10.1007/s11010-023-04848-3. Epub ahead of print. PMID: 37742314. https://link.springer.com/article/10.1007/s11010-023-04848-3 (Full text)

Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes

Abstract:

Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19.
We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT).
Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.
Source: Mrakic-Sposta S, Vezzoli A, Garetto G, Paganini M, Camporesi E, Giacon TA, Dellanoce C, Agrimi J, Bosco G. Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes. Metabolites. 2023; 13(10):1032. https://doi.org/10.3390/metabo13101032 https://www.mdpi.com/2218-1989/13/10/1032 (Full text)

Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents

Abstract:

SARS-CoV-2 infection causes transient cardiorespiratory and neurological disorders, and severe acute illness is rare among children. Post COVID-19 condition (PCC) may cause profound, persistent phenotypes with increasing prevalence. Its manifestation and risk factors remain elusive. In this monocentric study, we hypothesized that atopy, the tendency to produce an exaggerated immunoglobulin E (IgE) immune response, is a risk factor for the manifestation of pediatric PCC.
We present a patient cohort (n = 28) from an early pandemic period (2021–2022) with comprehensive evaluations of phenotypes, pulmonary function, and molecular investigations. PCC predominantly affected adolescents and presented with fatigue, dyspnea, and post-exertional malaise. Sensitizations to aeroallergens were found in 93% of cases.
We observed elevated IgE levels (mean 174.2 kU/L, reference < 100 kU/L) regardless of disease severity. Concurrent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) was found in 29% of patients that also faced challenges in school attendance. ME/CFS manifestation was significantly associated with elevated immunoglobulin G subclasses IgG3 (p < 0.05) and IgG4 (p < 0.05). A total of 57% of patients showed self-limiting disease courses with mean recovery at 12.7 months (range 5–25 months), 29% at 19.2 months (range 12–30 months), and the rest demonstrated overall improvement. These findings offer additional insights into immune dysregulation as a risk factor for pediatric PCC.
Source: Körner RW, Bansemir OY, Franke R, Sturm J, Dafsari HS. Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents. Children. 2023; 10(10):1598. https://doi.org/10.3390/children10101598 https://www.mdpi.com/2227-9067/10/10/1598 (Full text)

Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation

Abstract:

The long-term effects of COVID-19 on cognitive function have become an area of increasing concern. This paper provides an overview of characteristics, risk factors, possible mechanisms, and management strategies for cognitive dysfunction in post-COVID-19 condition (PCC).

Prolonged cognitive dysfunction is one of the most common impairments in PCC, affecting between 17% and 28% of the individuals more than 12 weeks after the infection and persisting in some cases for several years. Cognitive dysfunctions can be manifested as a wide range of symptoms including memory impairment, attention deficit, executive dysfunction, and reduced processing speed. Risk factors for developing PCC, with or without cognitive impairments, include advanced age, preexisting medical conditions, and the severity of acute illness. The underlying mechanisms remain unclear, but proposed contributors include neuroinflammation, hypoxia, vascular damage, and latent virus reactivation not excluding the possibility of direct viral invasion of the central nervous system, illustrating complex viral pathology.

As the individual variation of the cognitive impairments is large, a neuropsychological examination and a person-centered multidimensional approach are required. According to the World Health Organization, limited evidence on COVID-19-related cognitive impairments necessitates implementing rehabilitation interventions from established practices of similar conditions. Psychoeducation and compensatory skills training are recommended. Assistive products and environmental modifications adapted to individual needs might be helpful. In specific attention- and working memory dysfunctions, cognitive training—carefully monitored for intensity—might be effective for people who do not suffer from post-exertional malaise. Further research is crucial for evidence-based interventions specific to COVID-19-related cognitive impairments.

Source: Möller M, Borg K, Janson C, Lerm M, Normark J, Niward K. Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation. J Intern Med. 2023 Sep 27. doi: 10.1111/joim.13720. Epub ahead of print. PMID: 37766515. https://onlinelibrary.wiley.com/doi/10.1111/joim.13720 (Full text)