Category: Overlapping Illnesses

Rapid improvement in severe long COVID following perispinal etanercept

Abstract:

Background: This study aimed to describe the neurological improvements in a patient with severe long COVID brain dysfunction following perispinal etanercept administration. Perispinal administration of etanercept, a novel method designed to enhance its brain delivery via carriage in the cerebrospinal venous system, has previously been shown to reduce chronic neurological dysfunction after stroke. Etanercept is a recombinant biologic that is capable of ameliorating two components of neuroinflammation: microglial activation and the excess bioactivity of tumor necrosis factor (TNF), a proinflammatory cytokine that is a key neuromodulator in the brain. Optimal synaptic and brain network function require physiological levels of TNF. Neuroinflammation, including brain microglial activation and excess central TNF, can be a consequence of stroke or peripheral infection, including infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.

Methods: Standardized, validated measures, including the Montreal Cognitive Assessment, Beck Depression Index-II (BDI-II), Fatigue Assessment Scale, Controlled Oral Word Association Test, Trail Making Tests, Timed Finger-to-Nose Test, 20 meter Self-Paced Walk Test, 5 Times Sit-to-Stand Test and Grip Strength measured with a Jamar Dynamometer were used to quantitate changes in cognition, depression, fatigue and neurological function after a single 25mg perispinal etanercept dose in a patient with severe long COVID of 12 months duration.

Results: Following perispinal etanercept administration there was immediate neurological improvement. At 24 hours there were remarkable reductions in chronic post-COVID-19 fatigue and depression, and significant measureable improvements in cognition, executive function, phonemic verbal fluency, balance, gait, upper limb coordination and grip strength. Cognition, depression and fatigue were examined at 29 days; each remained substantially improved.

Conclusion: Perispinal etanercept is a promising treatment for the chronic neurologic dysfunction that may persist after resolution of acute COVID-19, including chronic cognitive dysfunction, fatigue, and depression. These results suggest that long COVID brain neuroinflammation is a potentially reversible pathology and viable treatment target. In view of the increasing unmet medical need, clinical trials of perispinal etanercept for long COVID are urgently necessary. The robust results of the present case suggest that perispinal etanercept clinical trials studying long COVID populations with severe fatigue, depression and cognitive dysfunction may have improved ability to detect a treatment effect. Positron emission tomographic methods that image brain microglial activation and measurements of cerebrospinal fluid proinflammatory cytokines may be useful for patient selection and correlation with treatment effects, as well as provide insight into the underlying pathophysiology.

Source: Tobinick E, Spengler RN, Ignatowski TA, Wassel M, Laborde S. Rapid improvement in severe long COVID following perispinal etanercept. Curr Med Res Opin. 2022 Jul 6:1-23. doi: 10.1080/03007995.2022.2096351. Epub ahead of print. PMID: 35791687.  https://pubmed.ncbi.nlm.nih.gov/35791687/

Functional decline, long term symptoms and course of frailty at 3-months follow-up in COVID-19 older survivors, a prospective observational cohort study

Abstract:

Background: Aging is one of the most important prognostic factors increasing the risk of clinical severity and mortality of COVID-19 infection. However, among patients over 75 years, little is known about post-acute functional decline.

Objective: The aim of this study was to identify factors associated with functional decline 3 months after COVID-19 onset, to identify long term COVID-19 symptoms and transitions between frailty statesafter COVID-19 onset in older hospitalized patients.

Methods: This prospective observational study included COVID-19 patients consecutively hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital. Functional decline, frailty status and long term symptoms were assessed at 3 month follow up. Functional status was assessed using the Activities of Daily Living simplified scale (ADL). Frailty status was evaluated using Clinical Frailty Scale (CFS). We performed multivariable analyses to identify factors associated with functional decline.

Results: Among the 318 patients hospitalized for COVID-19 infection, 198 were alive 3 months after discharge. At 3 months, functional decline occurred in 69 (36%) patients. In multivariable analysis, a significant association was found between functional decline and stroke (OR = 4,57, p = 0,003), history of depressive disorder (OR = 3,05, p = 0,016), complications (OR = 2,24, p = 0,039), length of stay (OR = 1,05, p = 0,025) and age (OR = 1,08, p = 0,028). At 3 months, 75 patients described long-term symptoms (49.0%). Of those with frailty (CFS scores ≥5) at 3-months follow-up, 30% were not frail at baseline. Increasing frailty defined by a worse CFS state between baseline and 3 months occurred in 41 patients (26.8%).

Conclusions: This study provides evidence that both the severity of the COVID-19 infection and preexisting medical conditions correlates with a functional decline at distance of the infection. This encourages practitioners to establish discharge personalized care plan based on a multidimensional geriatric assessment and in parallel on clinical severity evaluation.

Source: Prampart S, Le Gentil S, Bureau ML, Macchi C, Leroux C, Chapelet G, de Decker L, Rouaud A, Boureau AS. Functional decline, long term symptoms and course of frailty at 3-months follow-up in COVID-19 older survivors, a prospective observational cohort study. BMC Geriatr. 2022 Jun 30;22(1):542. doi: 10.1186/s12877-022-03197-y. PMID: 35768781. https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-022-03197-y (Full text)

The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study

Abstract:

Background: Symptoms of post-acute sequelae of COVID-19 (PASC) may improve following SARS-CoV-2 vaccination. However few prospective data that also explore the underlying biological mechanism are available. We assessed the effect of vaccination on symptomatology of participants with PASC, and compared antibody dynamics between those with and without PASC.

Methods: RECoVERED is a prospective cohort study of adult patients with mild to critical COVID-19, enrolled from illness onset. Among participants with PASC, vaccinated participants were exact-matched 1:1 on age, sex, obesity status and time since illness onset to unvaccinated participants. Between matched pairs, we compared the monthly mean numbers of symptoms over a 3-month follow-up period, and, using exact logistic regression, the proportion of participants who fully recovered from PASC. Finally, we assessed the association between PACS status and rate of decay of spike- and RBD-binding IgG titers up to 9 months after illness onset using Bayesian hierarchical linear regression.

Findings: Of 349 enrolled participants, 316 (90.5%) had ≥3 months of follow-up, of whom 186 (58.9%) developed PASC. Among 36 matched pairs with PASC, the mean number of symptoms reported each month during 3 months of follow-up were comparable between vaccinated and unvaccinated groups. Odds of full recovery from PASC also did not differ between matched pairs (OR 1.57 [95%CI 0.46-5.84]) within 3 months after the matched time-point. The median half-life of spike- and RBD-binding IgG levels were, in days (95%CrI), 233 (183-324) and 181 (147-230) among participants with PASC, and 170 (125-252) and 144 (113-196) among those without PASC, respectively.

Interpretation: Our study found no strong evidence to suggest that vaccination improves symptoms of PASC. This was corroborated by comparable spike- and RBD-binding IgG waning trajectories between those with and without PASC, refuting any immunological basis for a therapeutic effect of vaccination on PASC.

Source: Wynberg E, Han AX, Boyd A, van Willigen HDG, Verveen A, Lebbink R, van der Straten K, Kootstra N, van Gils MJ, Russell C, Leenstra T, de Jong MD, de Bree GJ, Prins M; RECoVERED Study Group. The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study. Vaccine. 2022 Jun 7:S0264-410X(22)00748-4. doi: 10.1016/j.vaccine.2022.05.090. Epub ahead of print. PMID: 35725782; PMCID: PMC9170535. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170535/ (Full text)

The Role of Acupuncture for Long COVID: Mechanisms and Models

Abstract:

Objective: To establish an evidence-based role for acupuncture as a safe and effective treatment for managing Long COVID in the integrative medical setting.

Background: COVID-19 progresses to a chronic state, termed Long COVID, in about 30% of cases with estimates as high as 40% for prolonged illness. Symptoms are diverse and range over several body systems, including unrelenting fatigue, persistent malaise, chronic pain, and mood changes. Early clinical reports suggest acupuncture can effectively address both symptoms and the underlying causes of Long COVID.

Evidence: Historically, acupuncture is well defined in Traditional Chinese Medicine writings to treat influenza-like febrile illnesses. Contemporary scientific literature and case studies support the value of acupuncture for symptoms associated with acute and chronic respiratory viral infections, such as influenza, including SARS and COVID-19. Recent reports provide early evidence of acupuncture’s effectiveness in managing Long COVID symptoms and may also have disease-modifying benefits.

Conclusion: Acupuncture is a viable adjunctive health care modality as part of a multidisciplinary approach for symptom control and disease management to improve quality of life in Long COVID patients. Since acupuncture may favorably modify the length and outcome of this condition, the model of acupuncture presented in this article warrants broader use in the integrative clinical setting and for further research.

Source: James E. Williams and Jacques Moramarco. Medical Acupuncture. Jun 2022.159-166.http://doi.org/10.1089/acu.2021.0090 https://www.liebertpub.com/doi/full/10.1089/acu.2021.0090 (Full text)

Neurological long-COVID in the outpatient clinic: Two subtypes, two courses

Abstract:

Introduction: Symptoms referable to central and peripheral nervous system involvement are often evident both during the acute phase of COVID-19 infection and during long-COVID. In this study, we evaluated a population of patients with prior COVID-19 infection who showed signs and symptoms consistent with neurological long-COVID.

Methods: We prospectively collected demographic and acute phase course data from patients with prior COVID-19 infection who showed symptoms related to neurological involvement in the long-COVID phase. Firstly, we performed a multivariate logistic linear regression analysis to investigate the impact of demographic and clinical data, the severity of the acute COVID-19 infection and hospitalization course, on the post-COVID neurological symptoms at three months follow-up. Secondly, we performed an unsupervised clustering analysis to investigate whether there was evidence of different subtypes of neurological long COVID-19.

Results: One hundred and nine patients referred to the neurological post-COVID outpatient clinic. Clustering analysis on the most common neurological symptoms returned two well-separated and well-balanced clusters: long-COVID type 1 contains the subjects with memory disturbances, psychological impairment, headache, anosmia and ageusia, while long-COVID type 2 contains all the subjects with reported symptoms related to PNS involvement. The analysis of potential risk-factors among the demographic, clinical presentation, COVID 19 severity and hospitalization course variables showed that the number of comorbidities at onset, the BMI, the number of COVID-19 symptoms, the number of non-neurological complications and a more severe course of the acute infection were all, on average, higher for the cluster of subjects with reported symptoms related to PNS involvement.

Conclusion: We analyzed the characteristics of neurological long-COVID and presented a method to identify well-defined patient groups with distinct symptoms and risk factors. The proposed method could potentially enable treatment deployment by identifying the optimal interventions and services for well-defined patient groups, so alleviating long-COVID and easing recovery.

Source: Grisanti SG, Garbarino S, Barisione E, Aloè T, Grosso M, Schenone C, Pardini M, Biassoni E, Zaottini F, Picasso R, Morbelli S, Campi C, Pesce G, Massa F, Girtler N, Battaglini D, Cabona C, Bassetti M, Uccelli A, Schenone A, Piana M, Benedetti L. Neurological long-COVID in the outpatient clinic: Two subtypes, two courses. J Neurol Sci. 2022 Jun 3;439:120315. doi: 10.1016/j.jns.2022.120315. Epub ahead of print. PMID: 35717880; PMCID: PMC9212262. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212262/ (Full text)

Detecting anti-SARS-CoV-2 antibodies in urine samples: A noninvasive and sensitive way to assay COVID-19 immune conversion

Abstract:

Serum-based ELISA (enzyme-linked immunosorbent assay) has been widely used to detect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, to date, no study has investigated patient urine as a biological sample to detect SARS-CoV-2 virus-specific antibodies. An in-house urine-based ELISA was developed using recombinant SARS-CoV-2 nucleocapsid protein.

The presence of SARS-CoV-2 antibodies in urine was established, with 94% sensitivity and 100% specificity for the detection of anti-SARS-CoV-2 antibodies with the urine-based ELISA and 88% sensitivity and 100% specificity with a paired serum-based ELISA. The urine-based ELISA that detects anti-SARS-CoV-2 antibodies is a noninvasive method with potential application as a facile COVID-19 immunodiagnostic platform, which can be used to report the extent of exposure at the population level and/or to assess the risk of infection at the individual level.

Source: Ludolf F, Ramos FF, Bagno FF, Oliveira-da-Silva JA, Reis TAR, Christodoulides M, Vassallo PF, Ravetti CG, Nobre V, da Fonseca FG, Coelho EAF. Detecting anti-SARS-CoV-2 antibodies in urine samples: A noninvasive and sensitive way to assay COVID-19 immune conversion. Sci Adv. 2022 May 13;8(19):eabn7424. doi: 10.1126/sciadv.abn7424. Epub 2022 May 13. PMID: 35559681; PMCID: PMC9106288. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106288/ (Full text)

Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors

Abstract:

Background: Severe clinical pictures and sequelae of COVID-19 disease are immune mediated and characterized by a ‘cytokine storm’. Skeletal muscle has emerged as a potent regulator of immune system function. The aim of the present study is to define the prevalence of sarcopenia among COVID-19 survivors and the negative impact of sarcopenia on the post-acute COVID-19 syndrome and its related risk factors.

Methods: A total of 541 subjects recovered from COVID-19 disease were enrolled in the Gemelli Against COVID-19 Post-Acute Care between April 2020 and February 2021. They underwent a multidisciplinary clinical evaluation and muscle strength and physical performance assessment.

Results: Mean age was 53.1 years (SD 15.2, range from 18 to 86 years), and 274 (51%) were women. The prevalence of sarcopenia was 19.5%, and it was higher in patients with a longer hospital stay and lower in patients who were more physically active and had higher levels of serum albumin. Patients with sarcopenia had a higher number of persistent symptoms than non-sarcopenic patients (3.8 ± 2.9 vs. 3.2 ± 2.8, respectively; P = 0.06), in particular fatigue, dyspnoea, and joint pain.

Conclusions: Sarcopenia identified according to the EWGSOP2 criteria is high in patients recovered from COVID-19 acute illness, particularly in those who had experienced the worst clinical picture reporting the persistence of fatigue and dyspnoea. Our data suggest that sarcopenia, through the persistence of inflammation, could be the biological substrate of long COVID-19 syndrome. Physical activity, especially if associated with adequate nutrition, seems to be an important protective factor.

Source: Martone AM, Tosato M, Ciciarello F, Galluzzo V, Zazzara MB, Pais C, Savera G, Calvani R, Marzetti E, Robles MC, Ramirez M, Landi F; Gemelli Against COVID-19 Post-Acute Care Team. Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors. J Cachexia Sarcopenia Muscle. 2022 Jun 14. doi: 10.1002/jcsm.12931. Epub ahead of print. PMID: 35698920. https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12931 (Full text)

Long-Term Symptoms of COVID-19: One-Year Follow-Up Study

Abstract:

Introduction: Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have been reported in several patients who recovered from the acute phase at different intervals. However, there has been largely unclear data regarding the full range of long-term sequelae of coronavirus disease 2019 (COVID-19) patients. This study aims to evaluate the prevalence of long COVID syndrome.

Methods: A long-term research was conducted in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to December 2021 in which 2,000 patients who had recovered from COVID-19 and had been discharged were included in the study. Symptoms were noted at the time of discharge and at follow-up after 12 months. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v. 22.0 (IBM Corporation, Armonk, New York, United States).

Results: The mean age of the participants was 43 ± 10 years, 801 (53.8%) males and 688 (46.2%) females. At the time of discharge, the most common symptom was fatigue (26.93%), followed by dyspnea (20.34%) and muscle pain (8.86%). The most common symptom on follow-up was fatigue (6.78%).

Conclusion: We strongly emphasize discussing and exploring further knowledge on the post-infection syndrome, with an aim to bring healthcare professionals’ attention to the importance of handling COVID patients, their counseling, warning for alarming signs, and a long-term follow-up with necessary investigations and treatment.

Source: Shivani F, Kumari N, Bai P, et al. (June 14, 2022) Long-Term Symptoms of COVID-19: One-Year Follow-Up Study. Cureus 14(6): e25937. doi:10.7759/cureus.25937 https://www.cureus.com/articles/91406-long-term-symptoms-of-covid-19-one-year-follow-up-study (Full text)

A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study

Abstract:

Health consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health challenge. Research on post-COVID-19 condition is expanding but, at present, no agreement exists on the health outcomes that should be measured in people living with the condition.

To address this gap, we conducted an international consensus study, which included a comprehensive literature review and classification of outcomes for post-COVID-19 condition that informed a two-round online modified Delphi process followed by an online consensus meeting to finalise the core outcome set (COS). 1535 participants from 71 countries were involved, with 1148 individuals participating in both Delphi rounds. Eleven outcomes achieved consensus for inclusion in the final COS: fatigue; pain; post-exertion symptoms; work or occupational and study changes; survival; and functioning, symptoms, and conditions for each of cardiovascular, respiratory, nervous system, cognitive, mental health, and physical outcomes. Recovery was included a priori because it was a relevant outcome that was part of a previously published COS on COVID-19.

The next step in this COS development exercise will be to establish the instruments that are most appropriate to measure these core outcomes. This international consensus-based COS should provide a framework for standardised assessment of adults with post-COVID-19 condition, aimed at facilitating clinical care and research worldwide.

Source: Munblit D, Nicholson T, Akrami A, Apfelbacher C, Chen J, De Groote W, Diaz JV, Gorst SL, Harman N, Kokorina A, Olliaro P, Parr C, Preller J, Schiess N, Schmitt J, Seylanova N, Simpson F, Tong A, Needham DM, Williamson PR; PC-COS project steering committee. A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study. Lancet Respir Med. 2022 Jun 14:S2213-2600(22)00169-2. doi: 10.1016/S2213-2600(22)00169-2. Epub ahead of print. PMID: 35714658; PMCID: PMC9197249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197249/ (Full text)

The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study

Abstract:

Background: Characterizing the post-COVID health conditions is helpful to direct patients to appropriate healthcare.

Aims: To describe the presence of symptoms in COVID-19 patients within 6 months after diagnosis and to investigate the associated factors in terms of reporting symptoms.

Methods: Data of DEU-COVIMER (a telephone interview-based COVID-19 follow-up center established in a tertiary care hospital) was analyzed for SARS-CoV-2 RNA positive participants aged ≥ 18 years from November 1st, 2020, to May 31st, 2021. Symptom frequencies were stratified by demographic and clinical characteristics at one, three, and 6 months after diagnosis. With the patients who had symptoms at baseline, generalized estimating equations were applied to identify the factors associated with reporting of symptoms.

Results: A total of 5610 patients agreed to participate in the study. Symptom frequency was 37.2%, 21.8%, and 18.2% for the first, third, and sixth months. Tiredness/fatigue, muscle or body aches, and dyspnea/difficulty breathing were the most common symptoms in all time frames. In multivariate analysis, older age, female gender (odds ratio OR 1.74, 95% confidence interval 1.57-1.93), bad economic status (OR 1.37, 1.14-1.65), current smoking (OR 1.15, 1.02-1.29), being fully vaccinated before COVID-19 (OR 0.53, 0.40-0.72), having more health conditions (≥ 3 conditions, OR 1.78, 1.33-2.37), having more symptoms (> 5 symptoms, OR 2.47, 2.19-2.78), and hospitalization (intensive care unit, OR 2.18, 1.51-3.14) were associated with reporting of symptoms.

Conclusions: This study identifies risk factors for patients who experience post-COVID-19 symptoms. Healthcare providers should appropriately allocate resources prioritizing the patients who would benefit from post-COVID rehabilitation.

Source: Emecen AN, Keskin S, Turunc O, Suner AF, Siyve N, Basoglu Sensoy E, Dinc F, Kilinc O, Avkan Oguz V, Bayrak S, Unal B. The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study. Ir J Med Sci. 2022 Jun 17:1–10. doi: 10.1007/s11845-022-03072-0. Epub ahead of print. PMID: 35715663; PMCID: PMC9205653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205653/ (Full text)