Category: Overlapping Illnesses

Case Study: COVID-19 Brain Fog or Auditory Processing Disorder?

A wide array of symptoms have been directly associated with COVID-19 following recovery, but they can also occur several weeks or months after the diagnosis. These include, but are not limited to, damage to the respiratory tract as well as decreased cognition and other brain functions. The nonmedical term used to describe these post-COVID-19 problems is “brain fog.”

The symptoms of brain fog are similar to mild cognitive impairment or, of interest to audiologists, an auditory processing disorder (APD). 2 COVID-19 has neurological consequences and affects specific areas of the brain, such as the cingulate cortex (i.e. emotions, memory, depression, and decision of action). 3 Brain fog is also associated with several symptoms related to hearing and communication, which can affect the accomplishment of routine daily tasks. Many of those can be mistaken for or coexist with APD symptoms. These include “difficulty attending or staying focused, difficulty concentrating, difficulty understanding or remembering instructions, language problems, short-term memory problems,” to mention a few. 2 However, what might appear as a brain fog case could be an undiagnosed or even a pre-existing APD issue. 2 Symptoms could include struggling to keep track of conversations, forgetfulness and memory issues, problems following directions, and several cognitive difficulties. 2

This report presents the case of a 31-year-old medical doctor who was diagnosed with COVID-19 in December 2020, and later identified with APD symptoms that are now commonly seen in post-COVID-19 brain fog patients. Auditory training following the Buffalo Model 4 resolved the patient’s chief complaints following 12 treatment sessions. This issue is one of many that could shed light on the great potential auditory training has in resolving brain fog complaints that overlap with what is commonly seen in APD patients, highlighting the concerns regarding COVID-19’s direct effects on auditory processing.

Source: Alexander, Angela Loucks AuD, MNZAS, CCC-A; DiSogra, Robert M. AuD; Abbas, Fatima BS; Braund, Stacey AuD, CCC-A; Spokes, Chelsea BSpHLSc, MClinAud. Case Study: COVID-19 Brain Fog or Auditory Processing Disorder?. The Hearing Journal 76(04):p 18,19,20,22,23,24, April 2023. | DOI: 10.1097/01.HJ.0000927332.17564.4e https://journals.lww.com/thehearingjournal/Fulltext/2023/04000/Case_Study__COVID_19_Brain_Fog_or_Auditory.2.aspx (Full text)

Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study

Abstract:

Objectives To investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to people without COVID-19.

Method A cohort was selected from German routine health care data covering 38.9 million individuals. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19.

Results In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases.

Conclusions SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.

Source: Falko Tesch, Franz Ehm, Annika Vivirito, Danny Wende, Manuel Batram, Friedrich Loser, Simone Menzer, Josephine Jacob, Martin Roessler, Martin Seifert, Barbara Kind, Christina König, Claudia Schulte, Tilo Buschmann, Dagmar Hertle, Pedro Ballesteros, Stefan Baßler, Barbara Bertele, Thomas Bitterer, Cordula Riederer, Franziska Sobik, Lukas Reitzle, Christa Scheidt-Nave, Jochen Schmitt. Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study. medRxiv 2023.01.25.23285014; doi:https://doi.org/10.1101/2023.01.25.23285014 (Full text)

Chronic cough in post-COVID syndrome: Laryngeal electromyography findings in vagus nerve neuropathy

Abstract:

Background: Despite being a new entity, there is a large amount of information on the characteristics of SARS-CoV-2 infection and the symptoms of the acute phase; however, there are still many unknowns about the clinical features and pathophysiology of post-COVID syndrome. Refractory chronic cough is one of the most prevalent symptoms and carries both a medical problem and a social stigma. Many recent studies have highlighted the role of SARS-CoV-2 neurotropism, but no studies have demonstrated vagus nerve neuropathy as a cause of persistent chronic cough or other COVID-19 long-term effects.

Objective: The main objective was to assess the involvement of the vagus nerve neuropathy as a cause of chronic cough and other post-COVID syndrome symptoms.

Material and methods: This was a single-center observational study with prospective clinical data collected from 38 patients with chronic cough and post-COVID-19 syndrome. Clinical characteristics and laryngeal electromyographic findings were analyzed.

Results: Clinical data from 38 patients with chronic cough after 12 weeks of the acute phase of COVID-19 infection were analyzed. Of these patients, 81.6% suffered from other post-COVID conditions and, 73.6% reported fluctuating evolution of symptoms. Laryngeal electromyography (LEMG) of the thyroarytenoid (TA) muscles and cricothyroid (CT) muscles was pathological in 76.3% of the patients. Of the patients with abnormal LEMG, chronic denervation was the most frequent finding (82.8%), 10.3% presented acute denervation signs, and 6.9% presented myopathic pattern in LEMG.

Conclusions: LEMG studies suggest the existence of postviral vagus nerve neuropathy after SARS-CoV-2 infection that could explain chronic cough in post-COVID syndrome.

Source: García-Vicente P, Rodríguez-Valiente A, Górriz Gil C, Márquez Altemir R, Martínez-Pérez F, López-Pajaro LF, et al. (2023) Chronic cough in post-COVID syndrome: Laryngeal electromyography findings in vagus nerve neuropathy. PLoS ONE 18(3): e0283758. https://doi.org/10.1371/journal.pone.0283758 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0283758 (Full text)

Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies

Abstract:

Objective: The objective of the current investigation was to examine associations between symptomatic COVID-19 history, neurocognitive function, and psychiatric symptoms using cognitive task performance, functional brain imaging, and a prospective population survey.

Methods: Study 1 was a laboratory study conducted between 3 May 2022 and 16 Nov 2022 involving 120 fully vaccinated community dwelling adults between 18 and 84 years of age (Mage = 31.96 (SD = 20.71), 63.3% female). In this cross-sectional study we examined the association between symptomatic COVID-19 infection history and performance on three computer tasks assessing cognitive function (Flanker interference, delay discounting and simple reaction time) and measured oxygen saturation within the prefrontal cortex using functional near infrared spectroscopy (fNIRS). Study 2 was a 2-wave population survey undertaken between 28 September 2021 and 21 March 2022, examining the prospective relationship between symptomatic COVID-19 and self-reported symptoms of cognitive dysfunction, depressive symptoms, anxiety symptoms, and agitation at 6-month follow up. The sample (N = 2,002, M age = 37.0, SD = 10.4; 60.8% female) was collected using a quota process to ensure equal numbers of vaccinated and unvaccinated individuals. Structural equation modelling with latent variables was performed on the population-level data, evaluating the fit of the proposed mediational model of symptomatic COVID-19 to psychiatric symptoms through cognitive dysfunction.

Results: Findings from Study 1 revealed significant effects of symptomatic COVID-19 history on Flanker interference and delay discounting. Effects on flanker performance were significantly stronger among older adult women (effect: 9.603, SE = 4.452, t = 2.157, p = .033), and were accompanied by task-related changes cerebral oxygenation at the right superior frontal gyrus (F (1, 143.1) = 4.729, p = .031). Additionally, those with a symptomatic COVID-19 infection history showed evidence of amplified delay discounting (coefficient = 0.4554, SE = 0.2208, t = 2.0629, p = .041). In Study 2, baseline symptomatic COVID-19 history was associated with self-reported cognitive dysfunction and a latent variable reflecting psychiatric symptoms of anxiety, depression and agitation at follow-up. Mediational analyses revealed evidence of cognitive mediation of clinically significant psychiatric outcomes: depression (indirect effect = 0.077, SE = 0.026, p = .003) and generalized anxiety (indirect effect = 0.060, SE = 0.021, p = .004).

Conclusions: Converging findings from laboratory and population survey data support the conclusion that symptomatic COVID-19 infection is associated with task-related, functional imaging and self-reported indices of cognitive dysfunction as well as psychiatric symptoms. In some cases, these findings appear to be more amplified among women than men, and among older women than younger.

Source: Hall PA, Ayaz H, Meng G, Hudson A, Sakib MN, Quah ACK, Agar TK, Lee JA, Boudreau C, Fong GT. Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies. Brain Behav Immun Health. 2023 Mar;28:100595. doi: 10.1016/j.bbih.2023.100595. Epub 2023 Jan 24. PMID: 36713476; PMCID: PMC9870612. https://www.sciencedirect.com/science/article/pii/S2666354623000091?via%3Dihub (Full study)

The original strain of SARS-CoV-2, the Delta variant, and the Omicron variant infect microglia efficiently, in contrast to their inability to infect neurons: Analysis using 2D and 3D cultures

Highlights:

  • None of the SARS-CoV-2 original, delta, or omicron strains can infect neurons.
  • The SARS-CoV-2 original, delta, and omicron strains can infect microglia.
  • The CNS cells differentiated from hiPSCs are useful to investigate the infectivity of the virus.

Abstract:

COVID-19 causes neurological damage, systemic inflammation, and immune cell abnormalities. COVID-19-induced neurological impairment may be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which directly infects cells of the central nervous system (CNS) and exerts toxic effects. Furthermore, SARS-CoV-2 mutations occur constantly, and it is not well understood how the infectivity of the virus to cells of the CNS changes as the virus mutates.

Few studies have examined whether the infectivity of cells of CNS – neural stem/progenitor cells (NS/PCs), neurons, astrocytes, and microglia – varies among SARS-CoV-2 mutant strains. In this study, therefore, we investigated whether SARS-CoV-2 mutations increase infectivity to CNS cells, including microglia.

Since it was essential to demonstrate the infectivity of the virus to CNS cells in vitro using human cells, we generated cortical neurons, astrocytes, and microglia from human induced pluripotent stem cells (hiPSCs). We added pseudotyped lentiviruses of SARS-CoV-2 to each type of cells, and then we examined their infectivity. We prepared three pseudotyped lentiviruses expressing the S protein of the original strain (the first SARS-CoV-2 discovered in the world), the Delta variant, and the Omicron variant on their envelopes and analyzed differences of their ability to infect CNS cells. We also generated brain organoids and investigated the infectivity of each virus.

The viruses did not infect cortical neurons, astrocytes, or NS/PCs, but microglia were infected by the original, Delta, and Omicron pseudotyped viruses. In addition, DPP4 and CD147, potential core receptors of SARS-CoV-2, were highly expressed in the infected microglia, while DPP4 expression was deficient in cortical neurons, astrocytes, and NS/PCs.

Our results suggest that DPP4, which is also a receptor for Middle East respiratory syndrome-coronavirus (MERS-CoV), may play an essential role in the CNS. Our study is applicable to the validation of the infectivity of viruses that cause various infectious diseases in CNS cells, which are difficult to sample from humans.

Source: Kase Y, Sonn I, Goto M, Murakami R, Sato T, Okano H. The original strain of SARS-CoV-2, the Delta variant, and the Omicron variant infect microglia efficiently, in contrast to their inability to infect neurons: Analysis using 2D and 3D cultures. Exp Neurol. 2023 Mar 11;363:114379. doi: 10.1016/j.expneurol.2023.114379. Epub ahead of print. PMID: 36914084; PMCID: PMC10008041. https://www.sciencedirect.com/science/article/pii/S0014488623000638?via%3Dihub (Full text)

Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior

Abstract:

Prion is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria.

Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation.

Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequent production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manisfestions post-acute viral infection.

Source: Stefano GB, Büttiker P, Weissenberger S, Anders M, Raboch J, Ptacek R, Kream RM. Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior. Cell Mol Neurobiol. 2023 Mar 28:1–6. doi: 10.1007/s10571-023-01342-8. Epub ahead of print. PMID: 36977809; PMCID: PMC10047479. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047479/ (Full text)

Association of Laparoscopically-confirmed Endometriosis with Long COVID: A Prospective Cohort Study

Abstract:

Background: Women are at greater risk than men of developing chronic inflammatory conditions and of developing ‘long COVID.’ However, few gynecologic health risk factors for long COVID have been identified. Endometriosis is a common gynecological disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiologic mechanisms proposed for long COVID. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID.

Objective: To investigate the association between history of endometriosis prior to SARS-CoV-2 infection and risk of long COVID.

Methods: We followed 46,579 women from two ongoing prospective cohort studies: the Nurses’ Health Study II and the Nurses’ Health Study 3, who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires prior to the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, PCR, or antibody test) and CDC-defined long-term COVID-19 symptoms (≥4 weeks) were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases).

Results: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation and 1598 (43.8%) reported experiencing long COVID symptoms. The majority of women were Non-Hispanic White (95.4%), with a median age of 59 years (interquartile range=44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID (adjusted RR=1.22, 95% CI=1.05-1.42), compared to those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID as having symptoms ≥8 weeks (RR=1.28, 95% CI=1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend that women <50 years may be at higher risk (<50 years, RR=1.37, 95% CI=1.00-1.88; ≥50 years, RR=1.19, 95% CI=1.01-1.41). Among persons who developed long COVID, women with endometriosis reported on average one additional long-term symptom compared to women without endometriosis.

Conclusions and relevance: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID. Health care providers should be aware of endometriosis history when treating patients for signs of persisting symptoms post-SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations.

Source: Wang S, Farland LV, Gaskins AJ, Mortazavi J, Wang YX, Tamimi RM, Rich-Edwards JW, Zhang D, Terry KL, Chavarro JE, Missmer SA. Association of Laparoscopically-confirmed Endometriosis with Long COVID: A Prospective Cohort Study. Am J Obstet Gynecol. 2023 Mar 25:S0002-9378(23)00177-1. doi: 10.1016/j.ajog.2023.03.030. Epub ahead of print. PMID: 36972892. https://pubmed.ncbi.nlm.nih.gov/36972892/ https://www.ajog.org/article/S0002-9378(23)00177-1/pdf (Full text available as PDF file)

Sleep Disorders in Post-COVID Syndrome: A Psychiatric or Neurological Problem?

Abstract:

The coronavirus pandemic that began in 2019 continues. COVID-19 adversely affects human health not only in the acute, but also in the long-term period of the disease: in a large percentage of cases, health is not fully restored after long periods, requires medical intervention, and is often difficult to correct.

Researchers noted during the first wave of the pandemic in 2020 that about 10-20% of patients did not fully recover by three weeks from disease onset and the possible duration of the recovery period remains insufficiently clear, as do the reasons for differences in course during this period. Prolonged recovery after viral infection is not a feature exclusive to COVID-19, which does not facilitate the management of patients with post-COVID syndrome (PCS).

The mental health impact of COVID-19 is significant, with at least 30% of recovered patients likely to have symptoms of anxiety and/or depression after the acute phase has passed. Since the onset of COVID-19, there has been an increase in sleep disorders by 42%, with every third COVID-19 survivor reporting sleep complaints. In PCS, this condition is referred to as coronasomnia.

The success of therapy for this condition depends on identifying and correcting patients’ mental disorders, as anxiety and depression are often accompanied by sleep disorders this results in a bidirectional interaction between mental disorders and sleep quality. This article presents data on the anti-anxiety drugs Noofen and Adaptol, which help to correct the manifestations of PCS with sleep disorders.

Source: Kotova OV, Medvedev VE, Poluektov MG, Belyaev AA, Akarachkova ES. Sleep Disorders in Post-COVID Syndrome: A Psychiatric or Neurological Problem? Neurosci Behav Physiol. 2023;53(1):16-20. doi: 10.1007/s11055-023-01385-w. Epub 2023 Mar 11. PMID: 36969358; PMCID: PMC10006556. https://link.springer.com/article/10.1007/s11055-023-01385-w (Full text available as PDF file)

 

How do long COVID patients perceive their current life situation and occupational perspective? Results of a qualitative interview study in Germany

Abstract:

Introduction: Many people experience persistent or new-onset symptoms such as fatigue or cognitive problems after an acute infection with COVID-19. This phenomenon, known as long COVID, impacts physical and mental wellbeing, and may affect perceived quality of life and occupational perspectives likewise. The aim of this study is to gain a deeper understanding of how people with long COVID experience health-related restrictions in their daily life and their occupational situation, and to identify key challenges they face.

Methods: Guided qualitative interviews were conducted with 25 people with long COVID. The interviews were transcribed according to Dresing/Pehl and Kuckartz and analyzed using qualitative content analysis. Afterward, a systematic comparison of the data and a reflection under consideration of lifeworld-theoretical approaches (Berger and Luckmann) were carried out.

Results: The interviews revealed that many participants have severe symptoms which strongly impair them in perform daily and work-related activities, and in their personal interests. Many interviewees already reach their stress limit during routine household activities or childcare. Of the 25 participants, 19 experienced limitations in pursuing leisure activities, and 10 of the 23 interviewees with jobs reported being on sick leave for several months. Several respondents who had vocational reintegration are still affected by ongoing symptoms that affect their work performance considerably. This leads to uncertainty, role conflicts, a decline in social contacts, and decreased incomes, which contribute to an impairment in their quality of life.

Conclusions: This study shows the huge need for specific support for people with long COVID in different areas of life. To prevent people with long COVID from finding themselves in social and economic precarity, decision-makers should develop strategies to systematically support them in their sustainable reintegration into the workforce. The focus should be on creating long COVID-sensitive workplaces, compensating for decreased incomes, and improving access to relief services such as vocational reintegration. We argue, that a shift of perspectives is necessary and that long COVID should be considered rather as a “social disease” with considerably impairments in the social life of those affected.

Trial registration: The study is registered in the German register for clinical trials (DRKS00026007).

Source: Schmachtenberg T, Müller F, Kranz J, Dragaqina A, Wegener G, Königs G, Roder S. How do long COVID patients perceive their current life situation and occupational perspective? Results of a qualitative interview study in Germany. Front Public Health. 2023 Mar 9;11:1155193. doi: 10.3389/fpubh.2023.1155193. PMID: 36969629; PMCID: PMC10034079. https://www.frontiersin.org/articles/10.3389/fpubh.2023.1155193/full (Full text)

Functional limitations in individuals with long COVID

Abstract:

Objectives: To examine the extent of long-term functional deficits experienced by individuals hospitalized for COVID-19. Specific objectives were to: 1. describe changes in perceived global health, mobility, participation in daily activities, and employment status from pre-COVID-19 to ≥2 months following infection; and 2. evaluate factors associated with change in function.

Design: We conducted a telephone survey (at least 2 months post infection).

Setting: Population-based study of adults living at home.

Participants: Adult residents in Laval, Quebec, who were discharged home post-hospitalization for COVID-19.

Interventions: Not applicable MAIN OUTCOME MEASURES: Participants responded to a standard questionnaire (Covid-19 Yorkshire Rehabilitation Screen) regarding persistent symptoms and limitations in daily functioning. We calculated the prevalence of changes in perceived global health, mobility, personal care, participation in daily activities, and employment and evaluated associated factors using bivariate analysis and multivariable logistic regression.

Results: Almost all participants (94%) were more fatigued and reported deterioration of their global health status (90%) at least three months after infection. The majority were more short of breath, and experienced pain and anxiety. The change in outcomes indicate a substantial reduction in those reporting ‘good’ health status, mobility, personal care, and daily activities, and less employment. Time since diagnosis was significantly associated with global health, mobility, and participation in daily activities.

Conclusion: This population-based study suggests that individuals hospitalized for COVID-19 infection have symptoms that impact daily functional activities many months after infection. It is imperative that the impact of infection is better understood so that those affected long-term can receive the needed services.

Source: Mazer B, Feldman DE. Functional limitations in individuals with long COVID. Arch Phys Med Rehabil. 2023 Mar 24:S0003-9993(23)00162-4. doi: 10.1016/j.apmr.2023.03.004. Epub ahead of print. PMID: 36966957; PMCID: PMC10036292. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036292/ (Full text)