Management and treatment of long COVID symptoms in general practices: An online-based survey

Abstract:

Independent from initial severity, many patients develop persistent symptoms after infection with SARS-CoV-2, described as long COVID syndrome. Most of these patients are treated by general practitioners (GPs). As evidence-based treatment recommendations are still sparse, GPs must make their therapy decisions under uncertainty.

We investigated (1) the most frequently observed long COVID symptoms in general practices and (2) GPs’ applied treatment and rehabilitation plans for these symptoms. In total, 143 German GPs participated in an online-based survey between 05/2021 and 07/2021. We found that each GP practice was treating on average 12 patients with long COVID symptoms. Most frequently seen symptoms were fatigue and reduced performance. Current therapy options were rated as poor and loss of smell and taste, fatigue, or lack of concentration were perceived to be especially difficult to treat. The use of drug and non-drug therapies and specialist referrals focused primarily on physiological and less on psychosomatic/psychological rehabilitation and followed guidelines of similar conditions.

Our results provide first insights into how GPs approach a newly emerging condition in the absence of guidelines, evidence-based recommendations, or approved therapies, and might inform about GP preparedness in future pandemics. Our results also emphasize a gap between the current knowledge of the long COVID manifestation and knowledge about effective rehabilitation.

Source: Schrimpf A, Braesigk A, Lippmann S, Bleckwenn M. Management and treatment of long COVID symptoms in general practices: An online-based survey. Front Public Health. 2022 Sep 13;10:937100. doi: 10.3389/fpubh.2022.937100. PMID: 36176520; PMCID: PMC9513068. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513068/ (Full text)

Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome

Abstract:

Background: The autonomic nervous system (ANS) is a complex network where sympathetic and parasympathetic domains interact inside and outside of the network. Correlation-based network analysis (NA) is a novel approach enabling the quantification of these interactions. The aim of this study is to assess the applicability of NA to assess relationships between autonomic, sensory, respiratory, cerebrovascular, and inflammatory markers on post-acute sequela of COVID-19 (PASC) and postural tachycardia syndrome (POTS).

Methods: In this retrospective study, datasets from PASC (n = 15), POTS (n = 15), and matched controls (n = 11) were analyzed. Networks were constructed from surveys (autonomic and sensory), autonomic tests (deep breathing, Valsalva maneuver, tilt, and sudomotor test) results using heart rate, blood pressure, cerebral blood flow velocity (CBFv), capnography, skin biopsies for assessment of small fiber neuropathy (SFN), and various inflammatory markers. Networks were characterized by clusters and centrality metrics.

Results: Standard analysis showed widespread abnormalities including reduced orthostatic CBFv in 100%/88% (PASC/POTS), SFN 77%/88%, mild-to-moderate dysautonomia 100%/100%, hypocapnia 87%/100%, and elevated inflammatory markers. NA showed different signatures for both disorders with centrality metrics of vascular and inflammatory variables playing prominent roles in differentiating PASC from POTS.

Conclusions: NA is suitable for a relationship analysis between autonomic and nonautonomic components. Our preliminary analyses indicate that NA can expand the value of autonomic testing and provide new insight into the functioning of the ANS and related systems in complex disease processes such as PASC and POTS.

Source: Novak P, Giannetti MP, Weller E, Hamilton MJ, Mukerji SS, Alabsi HS, Systrom D, Marciano SP, Felsenstein D, Mullally WJ, Pilgrim DM, Castells M. Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome. Neurol Sci. 2022 Sep 28:1–12. doi: 10.1007/s10072-022-06423-y. Epub ahead of print. PMID: 36169757; PMCID: PMC9517969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517969/ (Full text)

Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms

Abstract:

Coronavirus disease 2019 (COVID-19), represents an enormous new threat to our healthcare system and particularly to the health of older adults. Although the respiratory symptoms of COVID-19 are well recognized, the neurological manifestations, and their underlying cellular and molecular mechanisms, have not been extensively studied yet. Our study is the first one to test the direct effect of serum from hospitalised COVID-19 patients on human hippocampal neurogenesis using a unique in vitro experimental assay with human hippocampal progenitor cells (HPC0A07/03 C). We identify the different molecular pathways activated by serum from COVID-19 patients with and without neurological symptoms (i.e., delirium), and their effects on neuronal proliferation, neurogenesis, and apoptosis.

We collected serum sample twice, at time of hospital admission and approximately 5 days after hospitalization. We found that treatment with serum samples from COVID-19 patients with delirium (n = 18) decreased cell proliferation and neurogenesis, and increases apoptosis, when compared with serum samples of sex- and age-matched COVID-19 patients without delirium (n = 18). This effect was due to a higher concentration of interleukin 6 (IL6) in serum samples of patients with delirium (mean ± SD: 229.9 ± 79.1 pg/ml, vs. 32.5 ± 9.5 pg/ml in patients without delirium).

Indeed, treatment of cells with an antibody against IL6 prevented the decreased cell proliferation and neurogenesis and the increased apoptosis. Moreover, increased concentration of IL6 in serum samples from delirium patients stimulated the hippocampal cells to produce IL12 and IL13, and treatment with an antibody against IL12 or IL13 also prevented the decreased cell proliferation and neurogenesis, and the increased apoptosis. Interestingly, treatment with the compounds commonly administered to acute COVID-19 patients (the Janus kinase inhibitors, baricitinib, ruxolitinib and tofacitinib) were able to restore normal cell viability, proliferation and neurogenesis by targeting the effects of IL12 and IL13.

Overall, our results show that serum from COVID-19 patients with delirium can negatively affect hippocampal-dependent neurogenic processes, and that this effect is mediated by IL6-induced production of the downstream inflammatory cytokines IL12 and IL13, which are ultimately responsible for the detrimental cellular outcomes.

Source: Borsini, A., Merrick, B., Edgeworth, J. et al. Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01741-1  (Full text)

Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program

Abstract:

Importance: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations. Objective: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection.

Design, Settings, and Participants: Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C). Exposures: Pre-COVID-19 receipt of a complete vaccine series versus no pre-COVID-19 vaccination.

Main Outcomes and Measures: Two approaches to the identification of long COVID were used. In the clinical diagnosis cohort (n=47,752), ICD-10 diagnosis codes or evidence of a healthcare encounter at a long COVID clinic were used. In the model-based cohort (n=199,498), a computable phenotype was used. The association between pre-COVID vaccination and long COVID was estimated using IPTW-adjusted logistic regression and Cox proportional hazards.

Results: In both cohorts, when adjusting for demographics and medical history, pre-COVID vaccination was associated with a reduced risk of long COVID (clinic-based cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; model-based cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75).

Conclusions and Relevance: Long COVID has become a central concern for public health experts. Prior studies have considered the effect of vaccination on the prevalence of future long COVID symptoms, but ours is the first to thoroughly characterize the association between vaccination and clinically diagnosed or computationally derived long COVID. Our results bolster the growing consensus that vaccines retain protective effects against long COVID even in breakthrough infections.

Source: M Daniel BrannockRobert F ChewAlexander J PreissEmily C HadleyJulie A McMurryPeter J LeeseAndrew T GirvinMiles CrosskeyAndrea G ZhouRichard A MoffittMichele Jonsson FunkEmily PfaffMelissa HaendelChristopher G ChuteN3C ConsortiumRECOVER Consortium. Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program.

Rehabilitation in long COVID-19: A mini-review

Abstract:

We have been experiencing multiple waves of the coronavirus disease 2019 (COVID-19) pandemic. With these unprecedented waves, we have entered into an era of ‘new normal’. This pandemic has enforced us to rethink the very basics of childhood learning: Habits, health etiquette, and hygiene. Rehabilitation has immense importance during this pandemic considering a few aspects. Multidisciplinary COVID-19 rehabilitation clinics are essential to address the demand. The equitable distribution of COVID-19 rehabilitation services for differently-abled individuals during the pandemic is an important aspect. Rehabilitation needs identification and further studies on various rehabilitation interventions are among the key unmet future research needs.

Source: Swarnakar R, Yadav SL. Rehabilitation in long COVID-19: A mini-review. World J Methodol. 2022 Jul 20;12(4):235-245. doi: 10.5662/wjm.v12.i4.235. PMID: 36159093; PMCID: PMC9350732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350732/ (Full text)

An international study of post-COVID sleep health

Abstract:

Objectives: COVID-19 has infected millions of people worldwide, with growing evidence that individuals with a history of infection may continue to show persistent post-COVID symptoms (long COVID). The aim of this study was to investigate sleep health in an international sample of individuals who reported previously testing positive for COVID-19.

Design: Cross-sectional.

Setting: Online survey distributed online between March and June 2021.

Participants: A total of 1001 individuals who reported a positive diagnosis of COVID-19 across different geographical regions, including North and South America, Sub-Saharan Africa, and Europe.

Measurements: Self-reported sleep health, using the Regulatory Satisfaction Alertness Timing Efficiency Duration scale, as recalled before a COVID-19 diagnosis and also reported currently.

Results: Individuals reported worse overall current sleep health, with lower ratings across the 6 dimensions of sleep health (sleep regularity, satisfaction, alertness, timing, efficiency, and duration) compared to their ratings as recalled before COVID-19 infection. Greater severity of COVID-19 symptoms was the strongest predictor of poor current sleep health (P < .001), independent of demographics, presence of a pre-existing chronic health condition, and time since infection. Poor current sleep health was associated with poorer current quality of life (P < .001).

Conclusions: Poor current sleep health is evident in individuals with a history of COVID-19, particularly those with more severe symptoms at the time of their COVID-19 infection and is associated with a poorer quality of life. Clinicians and researchers should assess sleep health in COVID-19 patients and investigate long-term associations with their mental and physical health, as well as potential benefits of improving sleep in this population.

Source: Alzueta E, Perrin PB, Yuksel D, Ramos-Usuga D, Kiss O, Iacovides S, de Zambotti M, Cortes M, Olabarrieta-Landa L, Arango-Lasprilla JC, Baker FC. An international study of post-COVID sleep health. Sleep Health. 2022 Sep 23:S2352-7218(22)00112-7. doi: 10.1016/j.sleh.2022.06.011. Epub ahead of print. PMID: 36163137; PMCID: PMC9501615. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501615/ (Full text)

Post-COVID-19 Syndrome: A Novel Diagnosis

Abstract:

Patients with post-COVID-19 syndrome have reported a wide array of symptoms that include autonomic dysfunction. It is hypothesized that this may be secondary to interruption of baroreflex pathways in the carotid arteries or nucleus tractus solitarius, however, confirming studies have yet to be performed. A limited number of studies have highlighted the presence of an exaggerated baroreflex response in patients with a post-COVID-19 syndrome that mirror other chronic autonomic dysfunction-related conditions.

Source: Kalia R, Kalia R, Musih J, Cubelo M, Popat J. Post-COVID-19 Syndrome: A Novel Diagnosis. Cureus. 2022 Aug 22;14(8):e28266. doi: 10.7759/cureus.28266. PMID: 36158335; PMCID: PMC9491485. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491485/ (Full text)

Long COVID symptoms in a population-based sample of persons discharged home from hospital

Abstract:

Objectives: The impact of long COVID among persons hospitalized and discharged home is unknown. We aimed to (1) report the prevalence of long COVID in persons hospitalized for COVID-19 and discharged home; (2) estimate the prevalence of physical, sensory, and psychological/mental health impairments; and (3) explore associated factors.

Methods: We conducted a telephone survey of adult residents in Laval, Quebec, who were discharged home ≥ 2 months post-hospitalization for COVID-19. Participants responded to a standard questionnaire regarding persistent symptoms. We calculated the prevalence of long COVID and of persistent types of symptoms and evaluated associated factors using bivariate analysis and multivariable logistic regression.

Results: In our sample (n = 398), 70% reported physical symptoms, 58% psychological problems, and 16% sensory impairments. 31.5% reported being troubled by persistent symptoms (long COVID). Factors associated with long COVID were a greater number of symptoms (odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.69-2.28) and increased hospital stay (OR = 1.03, 95% CI = 1.01-1.06). Other factors associated with physical and psychological symptoms were female sex (OR = 2.17, 95% CI = 1.27-3.71 and OR = 2.06, 95% CI = 1.25-3.39; respectively), higher education level (OR = 2.10, 95% CI = 1.20-3.68 and OR = 2.43, 95% CI = 1.44-4.14; respectively), and obesity (OR = 1.95, 95% CI = 1.15-3.34 and OR = 1.70, 95% CI = 1.05-2.77; respectively).

Conclusion: In this population-based study of persons hospitalized for COVID-19 and discharged home, nearly one third were troubled by symptoms for 2 months or more post-discharge. There was a high proportion with persistent physical and psychological/mental health symptoms. Further research will assess the specific needs of these patients to inform health policy makers on service requirements for these persons.

Source: Feldman DE, Boudrias MH, Mazer B. Long COVID symptoms in a population-based sample of persons discharged home from hospital. Can J Public Health. 2022 Sep 21:1–10. doi: 10.17269/s41997-022-00695-9. Epub ahead of print. PMID: 36131218; PMCID: PMC9491248. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491248/ (Full text)

Investigating Topic Modeling Techniques to Extract Meaningful Insights in Italian Long COVID Narration

Abstract:

Through an adequate survey of the history of the disease, Narrative Medicine (NM) aims to allow the definition and implementation of an effective, appropriate, and shared treatment path. In the present study different topic modeling techniques are compared, as Latent Dirichlet Allocation (LDA) and topic modeling based on BERT transformer, to extract meaningful insights in the Italian narration of COVID-19 pandemic.

In particular, the main focus was the characterization of Post-acute Sequelae of COVID-19, (i.e., PASC) writings as opposed to writings by health professionals and general reflections on COVID-19, (i.e., non-PASC) writings, modeled as a semi-supervised task. The results show that the BERTopic-based approach outperforms the LDA-base approach by grouping in the same cluster the 97.26% of analyzed documents, and reaching an overall accuracy of 91.97%.

Source: Scarpino I, Zucco C, Vallelunga R, Luzza F, Cannataro M. Investigating Topic Modeling Techniques to Extract Meaningful Insights in Italian Long COVID Narration. BioTech (Basel). 2022 Sep 3;11(3):41. doi: 10.3390/biotech11030041. PMID: 36134915; PMCID: PMC9496775. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496775/ (Full text)

Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity?

Abstract:

Molecular mimicry between human and microbial/viral/parasite peptides is common and has long been associated with the etiology of autoimmune disorders provoked by exogenous pathogens. A growing body of evidence accumulated in recent years suggests a strong correlation between SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between the SARS-CoV-2 spike glycoprotein (S-protein) and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies.

A total of 14 pentapeptides shared by the SARS-CoV-2 S-protein, thyroid, pituitary, adrenal cortex autoantigens and beta-cells of the islets of Langerhans were identified, all of them belong to the immunoreactive epitopes of SARS-CoV-2. The discussion of the findings relates the results to the clinical correlates of COVID-19-associated autoimmune endocrinopathies. The most common of these illnesses is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to the marker autoantigens of this disease.

The most important in pathogenesis of severe COVID-19, according to the authors, may be autoimmunity against adrenals because their adequate response prevents excessive systemic action of the inflammatory mediators causing cytokine storm and hemodynamic shock. A critique of the antigenic mimicry concept is given with an assertion that peptide sharing is not a guarantee but only a prerequisite for provoking autoimmunity based on the molecular mimicry. The latter event occurs in carriers of certain HLA haplotypes and when a shared peptide is only used in antigen processing.

Source: Churilov LP, Normatov MG, Utekhin VJ. Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity? Pathophysiology. 2022 Aug 25;29(3):486-494. doi: 10.3390/pathophysiology29030039. PMID: 36136066; PMCID: PMC9504401. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504401/ (Full text)