Tag: covid-19

SGLT2 Inhibitors in Long COVID Syndrome: Is There a Potential Role?

Abstract:

The coronavirus disease (COVID)-19 has turned into a pandemic causing a global public health crisis. While acute COVID-19 mainly affects the respiratory system and can cause acute respiratory distress syndrome, an association with persistent inflammatory stress affecting different organ systems has been elucidated in long COVID syndrome (LCS).
Increased severity and mortality rates have been reported due to cardiophysiological and metabolic systemic disorders as well as multiorgan failure in COVID-19, additionally accompanied by chronic dyspnea and fatigue in LCS. Hence, novel therapies have been tested to improve the outcomes of LCS of which one potential candidate might be sodium–glucose cotransporter 2 (SGLT2) inhibitors.
The aim of this narrative review was to discuss rationales for investigating SGLT2 inhibitor therapy in people suffering from LCS. In this regard, we discuss their potential positive effects—next to the well described “cardio-renal-metabolic” conditions—with a focus on potential anti-inflammatory and beneficial systemic effects in LCS. However, potential beneficial as well as potential disadvantageous effects of SGLT2 inhibitors on the prevalence and long-term outcomes of COVID-19 will need to be established in ongoing research.
Source: Zimmermann P, Sourij H, Aberer F, Rilstone S, Schierbauer J, Moser O. SGLT2 Inhibitors in Long COVID Syndrome: Is There a Potential Role? Journal of Cardiovascular Development and Disease. 2023; 10(12):478. https://doi.org/10.3390/jcdd10120478 https://www.mdpi.com/2308-3425/10/12/478 (Full text)

Drawing the Line Between Postacute Sequelae of COVID-19 and Functional Neurologic Disorders A Daunting Clinical Overlap or Irrelevant Conundrum?

Abstract:

Coronavirus disease 2019 (COVID-19) is an acute infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in its multiple variants that classically presents with cough, fatigue, fever, headache, myalgias, and diarrhea. As vaccination becomes widely available and infection rates facilitate herd immunity across the globe, more attention has been given to long-term symptoms that may persist after the index infection, which include impairments in concentration, executive dysfunction, sensory disturbances, depression, anxiety, fatigue, and cough, among other symptoms classified under the umbrella term of postacute sequelae of SARS-CoV-2 infection (PASC).

Functional neurologic disorder (FND), also known as conversion disorder and functional neurologic symptom disorder, refers to the presence of one or more symptoms of altered voluntary motor or sensory function that are incompatible with and not better explained by a known neurological or medical condition that causes significant distress and functional impairment. Although the diagnosis of FND may not require the identification of an underlying psychological stressor, being diagnosed with an FND can worsen stigma and shift attention and resources away from other medical concerns that should be concomitantly addressed.

This review summarizes the literature on the overlapping nature and discrimination of PASC from FND in COVID-19 survivors. Based on this, we develop a treatment framework that targets unique domains of these complex overlapping presentations, following a multidisciplinary approach with an individualized treatment plan inclusive of physical and psychological interventions focused on functional rehabilitation.

Source: Sales, Paulo M.G. MD, MS∗; Greenfield, Melissa J. PsyD∗; Pinkhasov, Aaron MD†; Viswanathan, Ramaswamy MD, DrMedSc‡; Saunders, Ramotse MD§; Huremović, Damir MD, MPP∥. Drawing the Line Between Postacute Sequelae of COVID-19 and Functional Neurologic Disorders: A Daunting Clinical Overlap or Irrelevant Conundrum?. The Journal of Nervous and Mental Disease 211(12):p 882-889, December 2023. | DOI: 10.1097/NMD.0000000000001643 https://journals.lww.com/jonmd/abstract/2023/12000/drawing_the_line_between_postacute_sequelae_of.2.aspx

Long Covid Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation

Abstract:

Background: Long Covid (LC) is a multisystem clinical syndrome with Functional Disability (FD) and compromised Overall Health (OH). There is a lack of distinct clinical symptom clusters (phenotypes) identified in LC so far but there is emerging information on LC clinical severity types. This study explores the consistency of these clinical severity types over time and the relationship between Symptom Severity (SS), FD, and OH in the context of the clinical severity types in a prospective sample.

Methods: A purposive sample of LC patients recruited to the LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS (LOCOMOTION) study were assessed using the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) at two assessment time points. A cluster analysis for clinical severity types was undertaken at both time points using k-means partition using two, three, and four initial clusters and different starting values. Cluster analysis was also carried out to assess the presence of symptom phenotypes (symptom clusters).

Findings: Cross-sectional data was available for 759 patients with 356 patients completing C19-YRSm at the two assessment points. Mean age was 46·8 years (SD = 12·7), 69·4% were females, and median duration of LC symptoms at first assessment was 360 days (IQR 217 to 703 days). Cluster analysis revealed three distinct SS and FD clinical severity types – mild (N=96), moderate (N=422), and severe (N=241) – with no distinct symptom phenotypes. The three-level clinical severity pattern remained consistent over time between the two assessments, with 51% of patients switching the clinical severity type between the assessments. The fluctuation was independent of the LC severity and time between the assessments.

Interpretation: This is the first study in the literature to show the consistency of the three clinical severity types over time with patients also switching between severity types indicating the fluctuating nature of LC.

Source: Sivan, Manoj and Smith, Adam B. and Osborne, Thomas and Goodwin, Madeline and Lawrence, Román Rocha and Baley, Sareeta and Williams, Paul and Lee, Cassie and Davies, Helen and Balasundaram, Kumaran and Greenwood, Darren C., Long Covid Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation. Available at SSRN: https://ssrn.com/abstract=4642650 or http://dx.doi.org/10.2139/ssrn.4642650 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4642650 (Full text available as PDF file)

The association of insomnia with long COVID: An international collaborative study (ICOSS-II)

Abstract:

Objective: There is evidence of a strong association between insomnia and COVID-19, yet few studies have examined the relationship between insomnia and long COVID. This study aimed to investigate whether COVID-19 patients with pre-pandemic insomnia have a greater risk of developing long COVID and whether long COVID is in turn associated with higher incident rates of insomnia symptoms after infection.

Methods: Data were collected cross-sectionally (May-Dec 2021) as part of an international collaborative study involving participants from 16 countries. A total of 2311 participants (18-99 years old) with COVID-19 provided valid responses to a web-based survey about sleep, insomnia, and health-related variables. Log-binomial regression was used to assess bidirectional associations between insomnia and long COVID. Analyses were adjusted for age, sex, and health conditions, including sleep apnea, attention and memory problems, chronic fatigue, depression, and anxiety.

Results: COVID-19 patients with pre-pandemic insomnia showed a higher risk of developing long COVID than those without pre-pandemic insomnia (70.8% vs 51.4%; adjusted relative risk [RR]: 1.33, 95% confidence interval [CI]: 1.07-1.65). Among COVID-19 cases without pre-pandemic insomnia, the rates of incident insomnia symptoms after infection were 24.1% for short COVID cases and 60.6% for long COVID cases (p < .001). Compared with short COVID cases, long COVID cases were associated with an increased risk of developing insomnia symptoms (adjusted RR: 2.00; 95% CI: 1.50-2.66).

Conclusions: The findings support a bidirectional relationship between insomnia and long COVID. These findings highlight the importance of addressing sleep and insomnia in the prevention and management of long COVID.

Source: Chen SJ, Morin CM, Ivers H, Wing YK, Partinen M, Merikanto I, Holzinger B, Espie CA, De Gennaro L, Dauvilliers Y, Chung F, Yordanova J, Vidović D, Reis C, Plazzi G, Penzel T, Nadorff MR, Matsui K, Mota-Rolim S, Leger D, Landtblom AM, Korman M, Inoue Y, Hrubos-Strøm H, Chan NY, Bjelajac AK, Benedict C, Bjorvatn B. The association of insomnia with long COVID: An international collaborative study (ICOSS-II). Sleep Med. 2023 Dec;112:216-222. doi: 10.1016/j.sleep.2023.09.034. Epub 2023 Oct 24. PMID: 37922783. https://www.sciencedirect.com/science/article/abs/pii/S1389945723003672

Complement dysregulation is a predictive and therapeutically amenable feature of long COVID

Abstract:

Background Long COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is a hallmark of acute COVID-19 but has not been investigated as a potential determinant of long COVID.

Methods We quantified a series of complement proteins, including markers of activation and regulation, in plasma samples from healthy convalescent individuals with a confirmed history of infection with SARS-CoV-2 and age/ethnicity/gender/infection/vaccine-matched patients with long COVID.

Findings Markers of classical (C1s-C1INH complex), alternative (Ba, iC3b), and terminal pathway (C5a, TCC) activation were significantly elevated in patients with long COVID. These markers in combination had a receiver operating characteristic predictive power of 0.794. Other complement proteins and regulators were also quantitatively different between healthy convalescent individuals and patients with long COVID. Generalized linear modeling further revealed that a clinically tractable combination of just four of these markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power of 0.785.

Conclusions These findings suggest that complement biomarkers could facilitate the diagnosis of long COVID and further suggest that currently available inhibitors of complement activation could be used to treat long COVID.

Source: Kirsten Baillie, Helen E Davies, Samuel B K Keat, Kristin Ladell, Kelly L Miners, Samantha A Jones, Ermioni Mellou, Erik J M Toonen, David A Price, B Paul Morgan, Wioleta M Zelek. Complement dysregulation is a predictive and therapeutically amenable feature of long COVID.
medRxiv 2023.10.26.23297597; doi: https://doi.org/10.1101/2023.10.26.23297597 https://www.medrxiv.org/content/10.1101/2023.10.26.23297597v1.full-text (Full text)

Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles

Abstract:

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as “long COVID”. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms.

We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues.

In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

Source: Aschman, T., Wyler, E., Baum, O. et al. Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles. acta neuropathol commun 11, 193 (2023). https://doi.org/10.1186/s40478-023-01662-2 https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-023-01662-2 (Full text)

Severe mental illness, race/ethnicity, multimorbidity and mortality following COVID-19 infection: nationally representative cohort study

Abstract:

Background: The association of COVID-19 with death in people with severe mental illness (SMI), and associations with multimorbidity and ethnicity, are unclear.

Aims: To determine all-cause mortality in people with SMI following COVID-19 infection, and assess whether excess mortality is affected by multimorbidity or ethnicity.

Method: This was a retrospective cohort study using primary care data from the Clinical Practice Research Database, from February 2020 to April 2021. Cox proportional hazards regression was used to estimate the effect of SMI on all-cause mortality during the first two waves of the COVID-19 pandemic.

Results: Among 7146 people with SMI (56% female), there was a higher prevalence of multimorbidity compared with the non-SMI control group (n = 653 024, 55% female). Following COVID-19 infection, the SMI group experienced a greater risk of death compared with controls (adjusted hazard ratio (aHR) 1.53, 95% CI 1.39-1.68). Black Caribbean/Black African people were more likely to die from COVID-19 compared with White people (aHR = 1.22, 95% CI 1.12-1.34), with similar associations in the SMI group and non-SMI group (P for interaction = 0.73). Following infection with COVID-19, for every additional multimorbidity condition, the aHR for death was 1.06 (95% CI 1.01-1.10) in the SMI stratum and 1.16 (95% CI 1.15-1.17) in the non-SMI stratum (P for interaction = 0.001).

Conclusions: Following COVID-19 infection, patients with SMI were at an elevated risk of death, further magnified by multimorbidity. Black Caribbean/Black African people had a higher risk of death from COVID-19 than White people, and this inequity was similar for the SMI group and the control group.

Source: Das-Munshi J, Bakolis I, Bécares L, Dyer J, Hotopf M, Ocloo J, Stewart R, Stuart R, Dregan A. Severe mental illness, race/ethnicity, multimorbidity and mortality following COVID-19 infection: nationally representative cohort study. Br J Psychiatry. 2023 Nov;223(5):518-525. doi: 10.1192/bjp.2023.112. PMID: 37876350; PMCID: PMC7615273. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615273/ (Full text)

Chronic Fatigue and Dysautonomia following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers

Abstract:

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dysautonomia tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2 vaccination of healthy controls (N = 89; 71 females; mean/median age: 39/49 years) were compared with corresponding values of PACVS-affected persons (N = 191; 159 females; mean/median age: 40/39 years) exhibiting chronic fatigue/dysautonomia (≥three symptoms for ≥five months after the last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications.

Normal vaccination response encompassed decreases in 11 receptor antibodies (by 25-50%, p < 0.0001), increases in two receptor antibodies (by 15-25%, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p < 0.0001) by increased Angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/mL, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/mL, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/mL, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers.

Source: Semmler A, Mundorf AK, Kuechler AS, Schulze-Bosse K, Heidecke H, Schulze-Forster K, Schott M, Uhrberg M, Weinhold S, Lackner KJ, Pawlitzki M, Meuth SG, Boege F, Ruhrländer J. Chronic Fatigue and Dysautonomia following COVID-19 Vaccination Is Distinguished from Normal Vaccination Response by Altered Blood Markers. Vaccines (Basel). 2023 Oct 26;11(11):1642. doi: 10.3390/vaccines11111642. PMID: 38005974. https://www.mdpi.com/2076-393X/11/11/1642 (Full text)

Sequential activation of DNA viruses by the RNA virus SARS-CoV-2 in patients with long COVID syndrome

Abstract:

Background: Reactivation of Epstein-Barr virus (EBV) has been suggested to play role in long lasting multiorgan symptoms several months after the initial COVID-19 illness.
Purpose: The aim of our prospective study was to 1) to evaluate the reactivation of DNA viruses of EBV, Cytomegalovirus, Herpes simplex, Varicella zoster and Parvovirus-B19 by SARS-CoV-2 in patients with the diagnosis of long-COVID syndrome, 2) to investigate the effect of supposed virus reactivation on clinical conditions and long COVID syndromes.
Methods: Patients with long COVID syndrome were prospectively included into the Vienna PostCoV Registry between March 15th 2021 and September 30th 2021. – The time between COVID-19 infection and first clinical visit was 219±98 days (7±3 months). Clinical symptoms were documented and patients were divided into symptoms-oriented subgroups with dominantly respiratory, cardiovascular or neuropsychologic complaints. Qualitative and quantitative viral IgG and IgM titer of the selected DNA viruses of n=105 patients were compared with age and sex-matched healthy (non-infected, non-vaccinated, n=105) controls, who had neither spike- nor nucleocapsid antibodies, nor clinical history of COVID-19 disease.
Results: Long Covid patients had significantly higher cumulative number of IgM positivity of the DNA viruses (18.1% vs 6.7%, p=0.02), and significantly elevated quantitative EBV IgG (420±296 vs 339±282 mg/dL, p=0.033) and Parvo-B19 IgM (0.28±0.29 vs 0.03±0.12 mg/dL, p<0.001) titer as compared to healthy controls. Significantly more patients with long COVID symptoms had an EBV IgG titer above the detection limit as compared with healthy controls (40% vs 28%, p=0.018), suggesting EBV virus reactivation and chronic EBV infection. EBV IgG titer was significantly higher in patients with dominant respiratory symptoms, while elevated Parvo-B19 IgM titer was observed in patients with dominant cardiovascular complaints. In patients with long-COVID syndrome the quantitative EBV IgG titer increased with the time between infection and blood sampling (logarithmic correlation, p=0.011), suggesting the subclinical continuous EBV activation by the SARS-CoV2 RNA virus, while the quantitative Parvo-B19 IgM titer decreased linearly during the observation period
Conclusions: In this study of patients with long-COVID syndrome, SARS-CoV-2 infection apparently activated certain types of DNA viruses (EBV, and Parvo-B19), as demonstrated by the significantly higher incidence of cumulative IgM positivity, and elevated EBV IgG and parvovirus-B19 IgM titers, in long-COVID patients compared to healthy controls.
Source: M Gyongyosi, E Hasimbegovic, D Lukovic, K Zlabinger, A Spannbauer, E Samaha, J Bergler-Klein, C Hengstenberg, P Mucher, H Haslacher, M Breuer, R Strassl, M Riesenhuber, C Nitsche, T A Zelniker, Sequential activation of DNA viruses by the RNA virus SARS-CoV-2 in patients with long COVID syndrome, European Heart Journal, Volume 44, Issue Supplement_2, November 2023, ehad655.1823, https://doi.org/10.1093/eurheartj/ehad655.1823 https://academic.oup.com/eurheartj/article/44/Supplement_2/ehad655.1823/7393979 (Full text available as PDF file)

Risk Factors for Long COVID in Older Adults

Abstract:

As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating. Within this context, the elderly population has not only become susceptible and high-risk during the acute phase of COVID-19 but also has considerable risks when confronting long COVID.
Elderly individuals possess specific immunological backgrounds, and during the process of aging, their immune systems can enter a state known as “immunosenescence”. This further exacerbates “inflammaging” and the development of various comorbidities in elderly individuals, rendering them more susceptible to long COVID. Additionally, long COVID can inflict both physical and mental harm upon elderly people, thereby reducing their overall quality of life. Consequently, the impact of long COVID on elderly people should not be underestimated.
This review seeks to summarize the infection characteristics and intrinsic factors of older adults during the COVID-19 pandemic, with a focus on the physical and mental impact of long COVID. Additionally, it aims to explore potential strategies to mitigate the risk of long COVID or other emerging infectious diseases among older adults in the future.
Source: Hu Y, Liu Y, Zheng H, Liu L. Risk Factors for Long COVID in Older Adults. Biomedicines. 2023; 11(11):3002. https://doi.org/10.3390/biomedicines11113002 https://www.mdpi.com/2227-9059/11/11/3002 (Full text)