Tag: long covid symptoms

Diagnostic challenges posed by intersections between post-acute covid syndrome and neurocognitive disorders

Introduction:

COVID-19 initially was considered an acute respiratory illness. Its severity was classified on the basis of symptoms of respiratory distress for example, tachypnoea and hypoxia. Accordingly, 80% cases reported asymptomatic or mild illness, about 5–15% being moderate severity and the last 5% requiring hospital-based care (COVID, 2021). Almost everyone was expected to tide over the infection in a couple of weeks. In the acute phase of the illness, central nervous system (CNS) involvement manifests as headaches, confusion, cerebrovascular events like strokes, dizziness and seizures (Wang et al., 2020–Pezzini et al., 2020). Infecting cells bearing the ACE- 2 receptor, it involves multiple organ systems, some of which are now known to run a chronic course. Its understanding as an acute infection has changed as more and more persons now report persistent symptoms running over months (Revised Guidelines on Clinical Management, 2021).

Studies report that between 30% and 40% of those recovered from COVID-19 infections report of lasting symptoms (Chopra et al., 2021). Accurate estimates of persons suffering from Post Acute Covid Syndrome (PACS) are unreliable as yet considering ongoing community transmissions and limitations in health care access. With over 215 million reported cases (coronavirus.jhu.edu, 2021), numbers of those with PACS can overrun any health system. Symptoms persisting beyond 4 weeks after recovery from acute infection range from chest pain and palpitations, shortness of breath, muscle and joint aches and pains, headaches, neuropathy and paraesthesia, fatigue, anosmia, ageusia, myalgia, cardiopulmonary insufficiency, increased propensity for thromboembolic phenomena, micro vascular coagulopathies, demyelinating conditions, cognitive dysfunctions, psychological distress and even sleep and mood disturbances. Collectively, these neuropsychiatric symptoms are sometimes referred to as “brain fog” and can be incapacitating. It is also unclear how long these symptoms will last.

Pathophysiology of COVID-19 related complications is largely unknown. Current research suggests that the chronic inflammation and aberrant immune responses in the host can be a cause of chronic inflammation, resulting in long-term neuropsychiatric symptoms (weeks – months post-acute infection) (Bechter, 2013). Inflammatory markers take much longer to return to pre morbid levels: correlations with PACS are however unclear. Data from the National Survey of Residential Care Facilities in the United States showed that 70% of individuals in these facilities had some cognitive issues, out of which 29% had mild and 19% had severe cognitive impairment (Zimmerman et al., 2014). Coronavirus infection outbreaks in the past like for Severe Acute Respiratory Syndrome (2002–04) and Middle East Respiratory Syndrome (2012) have also had neuropsychiatric symptoms: depressed mood, anxiety, insomnia, irritability, and memory impairments were noted. Psychological factors may also contribute to the development of some long term neuropsychiatric symptoms.

Roughly, 10% of the current global population is aged 65 or older (United Nations, 2021). Estimates of people living with neurocognitive disorder (NCDs) hover around 50 million worldwide with 10 million new cases added yearly. Globally, 80% of the deaths attributable to COVID-19 infections have occurred amongst persons 65 or older: however, age disaggregated data for COVID-19 infection, survival, lasting morbidity and mortality are unavailable.

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Source: Philip S, Shoib S, Gregor Issac T, Javed S. Diagnostic challenges posed by intersections between post-acute covid syndrome and neurocognitive disorders. Asian J Psychiatr. 2022 Jan;67:102936. doi: 10.1016/j.ajp.2021.102936. Epub 2021 Nov 21. PMID: 34844177; PMCID: PMC8606183. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606183/ (Full text)

Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC)

Introduction:

The emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought with it a plethora of new challenges. In the beginning of the pandemic, efforts were focused on pathogenesis and acute treatment; however, over time, understanding and managing post-COVID sequelae have become the new frontier.1, 2 Generally, the majority of individuals show symptom resolution within 3–4 weeks of COVID-19, but a substantial number of people continue to experience lingering effects and develop protracted illness, regardless of initial symptom severity. Although still being defined, these effects can be collectively referred to as postacute sequelae of SARS-CoV-2 infection (PASC),3 which is the term used in this report. Notably, there are a number of other terms that are found in the literature (eg, long COVID, postacute COVID-19 syndrome, long-haul COVID, chronic COVID). At the time of development, much of the literature focused on patients who were not vaccinated, and the incidence and trajectory of PASC in vaccinated patients with “breakthrough” cases (including but not limited to current and emerging variants of the virus) are evolving. The PASC Collaborative took this into account during the development process and these guidance statements generally apply to individuals who develop PASC regardless of their vaccination status.

This guidance statement has a specific focus on the cognitive-related symptoms of PASC that can occur in people who have been diagnosed with acute COVID-19 infection or presumed to have had the infection and initially experienced mild to severe symptoms. Some patients required hospital acute care, whereas many others were managed in nonhospitalized community settings. This consensus guidance statement is one in a series extending across the breadth of the most prevalent or recognized PASC sequelae. Published and in-process guidance statements from this collaborative include the assessment and management of PASC associated fatigue, breathing and respiratory sequelae, cardiovascular complications, autonomic dysfunction, mental health, and neurologic sequelae. These statements are intended to provide consensus-driven practice guidance to clinicians in the assessment and treatment of individuals presenting with PASC.

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Source: Fine JS, Ambrose AF, Didehbani N, Fleming TK, Glashan L, Longo M, Merlino A, Ng R, Nora GJ, Rolin S, Silver JK, Terzic CM, Verduzco-Gutierrez M, Sampsel S. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R. 2022 Jan;14(1):96-111. doi: 10.1002/pmrj.12745. Epub 2022 Jan 12. PMID: 34902226. https://onlinelibrary.wiley.com/doi/10.1002/pmrj.12745 (Full text)

Self-reported olfactory and gustatory dysfunctions in COVID-19 patients: a 1-year follow-up study in Foggia district, Italy

Abstract:

Background: From the initial stages of the pandemic in early 2020, COVID-19-related olfactory and gustatory dysfunctions have been widely reported and are emerging as one of the most frequent long-term sequelae of SARS-CoV-2 infection. However, data regarding the long-term recovery of the sense of smell and taste are lacking. This study aimed to characterize the evolution up to one year after the diagnosis of self-reported olfactory and gustatory dysfunctions in COVID-19 cases.

Methods: Based on the data of the active surveillance platform of the Apulia region, Italy, we selected the residents of Foggia district who were confirmed positive for SARS-CoV-2 from March 1st to June 16th, 2020, and home-quarantined with paucisymptomatic-to-mild clinical presentation. Self-reported olfactory and gustatory dysfunctions were recorded at baseline through a survey of dichotomous questions. The evolution of these symptoms at approximately one year was prospectively assessed via telephone by the validated sino-nasal outcome test 22 (SNOT-22, Italian version).

Results: Among the 1,175 COVID-19 cases notified in the Foggia district during the first epidemic wave, 488 had paucisymptomatic-to-mild clinical presentation. Of these, 41.2% (n = 201, 95% confidence interval [CI] 36.8-45.7%) reported at least one sensory dysfunction. A total of 178 to 201 (88.5%) patients agreed to participate in the follow-up survey. According to the SNOT-22 results, the persistence of a sensory dysfunction was observed in the 29.8% (n = 53, 95% CI 23.2-37.1%) of them. Particularly, loss of smell persisted in 25.8% (n = 46, 95% CI 19.6-32.9%), loss of taste in 21.3% (n = 38, 95% CI 15.6-28.1%), loss of both in 17.4% (n = 31, 95% CI 12.2-23.8%) of participants in the follow-up. The rates of full recovery increased over time: from 59% at 30 days to 71.9% at 90 days for the sense of smell; from 61.3% at 30 days to 74.7% at 90 days for the sense of taste.

Conclusions: The persistence of COVID-19-related olfactory and gustatory dysfunctions up to 12 months after the disease onset in a noteworthy proportion (approximately 3 out of 10) of patients with paucisymptomatic-to-mild clinical presentation deserves further investigations due to its possible pathophysiological implications and impact on the quality of life.

Source: Fortunato F, Martinelli D, Iannelli G, Milazzo M, Farina U, Di Matteo G, De Nittis R, Ascatigno L, Cassano M, Lopalco PL, Prato R. Self-reported olfactory and gustatory dysfunctions in COVID-19 patients: a 1-year follow-up study in Foggia district, Italy. BMC Infect Dis. 2022 Jan 22;22(1):77. doi: 10.1186/s12879-022-07052-8. PMID: 35065619; PMCID: PMC8783175. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783175/ (Full text)

Long COVID-19: Objectifying most self-reported neurological symptoms

Abstract:

Objectives: We aimed to objectify and compare persisting self-reported symptoms in initially hospitalized and non-hospitalized patients after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by applying clinical standardized measures.

Methods: We conducted a cross-sectional study of adult patients with confirmed SARS-CoV-2 infection including medical history, neurological examination, blood markers, neuropsychological testing, patient-reported outcome measures (PROMs), and brain magnetic resonance imaging (MRI).

Results: Fifty patients with persisting symptoms for at least 4 weeks were included and classified by initial hospitalization status. Median time from SARS-CoV-2 detection to investigation was 29.3 weeks (range 3.3-57.9). Although individual cognitive performance was generally within the normative range in both groups, mostly mild deficits were found in attention, executive functions, and memory. Hospitalized patients performed worse in global cognition, logical reasoning, and processes of verbal memory. In both groups, fatigue severity was associated with reduced performance in attention and psychomotor speed tasks (rs = -0.40, p < 0.05) and reduced quality of life (EQ5D, rs = 0.57, p < 0.001) and with more persisting symptoms (median 3 vs. 6, p < 0.01). PROMs identified fatigue, reduced sleep quality, and increased anxiety and depression in both groups but more pronounced in non-hospitalized patients. Brain MRI revealed microbleeds exclusively in hospitalized patients (n = 5).

Interpretation: Regardless of initial COVID-19 severity, an individuals’ mental and physical health can be severely impaired in the long-term limitedly objectified by clinical standard diagnostic with abnormalities primarily found in hospitalized patients. This needs to be considered when planning rehabilitation therapies and should give rise to new biomarker research.

Source: Bungenberg J, Humkamp K, Hohenfeld C, Rust MI, Ermis U, Dreher M, Hartmann NK, Marx G, Binkofski F, Finke C, Schulz JB, Costa AS, Reetz K. Long COVID-19: Objectifying most self-reported neurological symptoms. Ann Clin Transl Neurol. 2022 Jan 20. doi: 10.1002/acn3.51496. Epub ahead of print. PMID: 35060361. https://onlinelibrary.wiley.com/doi/10.1002/acn3.51496 (Full text) See PDF file HERE.

Post-acute neurological consequences of COVID-19: an unequal burden

COVID-19 and its neurological consequences particularly burden marginalized communities, and so can only be effectively treated by advancing health equity.

Our world has witnessed over 275 million confirmed cases of COVID-19 and over 5 million related deaths1. Marginalized communities everywhere continue to be disproportionately affected as the pandemic amplifies longstanding health and healthcare disparities. As an example, in the United States, members of the Black, Indigenous and Latino communities remain two to three times more likely to be infected with SARS-CoV-2, to be hospitalized with COVID-19 and to die from this disease2. Dismantling structural racism is necessary to improve neurological health, as greater attention is focused on understanding and addressing the post-acute neurological consequences of COVID-19, or the neurological manifestations of what is sometimes called long COVID.

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Source: Nolen, L.T., Mukerji, S.S. & Mejia, N.I. Post-acute neurological consequences of COVID-19: an unequal burden. Nat Med 28, 20–23 (2022). https://doi.org/10.1038/s41591-021-01647-5  (Full text)

Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing

Abstract:

Background: Some patients with COVID-19 who have recovered from the acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that often is unexplained by conventional investigative studies.

Research question: What is the pathophysiologic mechanism of exercise intolerance that underlies the post-COVID-19 long-haul syndrome in patients without cardiopulmonary disease?

Study design and methods: This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 patients who recovered from COVID-19 and were without cardiopulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results with those from 10 age- and sex-matched control participants. These data then were used to define potential reasons for exertional limitation in the cohort of patients who had recovered from COVID-19.

Results: The patients who had recovered from COVID-19 exhibited markedly reduced peak exercise aerobic capacity (oxygen consumption [VO2]) compared with control participants (70 ± 11% predicted vs 131 ± 45% predicted; P < .0001). This reduction in peak VO2 was associated with impaired systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen content difference to arterial oxygen content ratio) compared with control participants (0.49 ± 0.1 vs 0.78 ± 0.1; P < .0001), despite a preserved peak cardiac index (7.8 ± 3.1 L/min vs 8.4±2.3 L/min; P > .05). Additionally, patients who had recovered from COVID-19 demonstrated greater ventilatory inefficiency (ie, abnormal ventilatory efficiency [VE/VCO2] slope: 35 ± 5 vs 27 ± 5; P = .01) compared with control participants without an increase in dead space ventilation.

Interpretation: Patients who have recovered from COVID-19 without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit, along with an exaggerated hyperventilatory response during exercise.

Source: Singh I, Joseph P, Heerdt PM, Cullinan M, Lutchmansingh DD, Gulati M, Possick JD, Systrom DM, Waxman AB. Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing. Chest. 2022 Jan;161(1):54-63. doi: 10.1016/j.chest.2021.08.010. Epub 2021 Aug 11. PMID: 34389297; PMCID: PMC8354807.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354807/ (Full text)

Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study

Abstract:

This multicenter cohort study investigated the differences between coronavirus disease 2019 (COVID-19) related symptoms and post-COVID symptoms between male and female COVID-19 survivors. Clinical and hospitalization data were collected from hospital medical records in a sample of individuals recovered from COVID-19 at five public hospitals in Spain. A predefined list of post-COVID symptoms was systematically assessed, but patients were free to report any symptom. Anxiety/depressive levels and sleep quality were also assessed.
Adjusted multivariate logistic regressions were used to identify the association of sex with post-COVID related-symptoms. A total of 1969 individuals (age: 61, SD: 16 years, 46.4% women) were assessed 8.4 months after discharge. No overall significant sex differences in COVID-19 onset symptoms at hospital admission were found. Post-COVID symptoms were present in up to 60% of hospitalized COVID-19 survivors eight months after the infection. The number of post-COVID symptoms was 2.25 for females and 1.5 for males.
After adjusting by all variables, female sex was associated with ≥3 post-COVID symptoms (adj OR 2.54, 95%CI 1.671–3.865, p < 0.001), the presence of post-COVID fatigue (adj OR 1.514, 95%CI 1.040–2.205), dyspnea (rest: adj OR 1.428, 95%CI 1.081–1.886, exertion: adj OR 1.409, 95%CI 1.109–1.791), pain (adj OR 1.349, 95%CI 1.059–1.720), hair loss (adj OR 4.529, 95%CI 2.784–7.368), ocular problems (adj OR 1.981, 95%CI 1.185–3.312), depressive levels (adj OR 1.606, 95%CI 1.002–2.572) and worse sleep quality (adj OR 1.634, 95%CI 1.097–2.434). Female sex was a risk factor for the development of some long-term post-COVID symptoms including mood disorders. Healthcare systems should consider sex differences in the management of long haulers.
Source: Fernández-de-Las-Peñas C, Martín-Guerrero JD, Pellicer-Valero ÓJ, Navarro-Pardo E, Gómez-Mayordomo V, Cuadrado ML, Arias-Navalón JA, Cigarán-Méndez M, Hernández-Barrera V, Arendt-Nielsen L. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J Clin Med. 2022 Jan 14;11(2):413. doi: 10.3390/jcm11020413. PMID: 35054108; PMCID: PMC8778106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778106/ (Full text)
Source:

“LONG COVID”-A hypothesis for understanding the biological basis and pharmacological treatment strategy

Abstract:

Infection of humans with SARS-CoV-2 virus causes a disease known colloquially as “COVID-19” with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE-2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, “brain fog,” insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named “LONG COVID.”

Longitudinal clinical studies in a group of subjects who were infected with SARS-CoV-2 have been compared to a non-infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self-report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively.

It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid-derived 2-like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re-purposing studies in “LONG COVID” subjects experiencing insomnia, depression, fatigue, and “brain fog” but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.

Source: Jarrott B, Head R, Pringle KG, Lumbers ER, Martin JH. “LONG COVID”-A hypothesis for understanding the biological basis and pharmacological treatment strategy. Pharmacol Res Perspect. 2022 Feb;10(1):e00911. doi: 10.1002/prp2.911. PMID: 35029046. https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.911 (Full text)

“I feel like my body is broken”: Exploring the experiences of people living with long COVID

Abstract:

Background: Long COVID, an illness affecting a subset of individuals after COVID-19, is distressing and poorly understood. Exploring the experiences of people with long COVID could help inform current conceptualizations of the illness, guide supportive care strategies, and validate patients’ perspectives on the condition. Thus, the objective of this study was to better understand and explore individuals’ experiences with long COVID and commonly reported symptoms, using qualitative data collected from open-ended survey responses.

Methods: Data were collected from adults living with long COVID following a confirmed or suspected SARS-CoV-2 infection who participated in a larger observational, online survey. Within the larger survey, participants had the option of answering seven open-ended items. Data from the open-ended items were analyzed following guidelines for reflective thematic analysis.

Results: From the 213 who were included in the online survey, 169 participants who primarily self-identified as women (88.2%), aged 40-49 (33.1%), and who had been experiencing long COVID symptoms for ≥ 6 months (58.6%) responded to the open-ended questions. Four overlapping and interconnected themes were identified: (1) My long COVID symptoms are numerous, hard to describe, and debilitating, (2) All aspects of my day-to-day functioning have been impacted, (3) I can no longer be physically active, and (4) I keep asking for help, but no one is listening, and very little is working.

Conclusion: Findings highlight the complex nature of long COVID and show the ways in which individuals affected by the illness are negatively impacted. Participants recounted struggling and altering their daily activities while managing relapsing-remitting symptoms, an uncertain prognosis, lost pre-COVID identities, and a healthcare system (that does not always offer guidance nor take them seriously). More support and recognition for the condition are needed to help this cohort navigate the process of adapting to long COVID.

Source: Amanda Wurz, S. Nicole Culos-Reed, Kelli Franklin, Jessica DeMars, James G. Wrightson, Rosie Twomey. “I feel like my body is broken”: Exploring the experiences of people living with long COVID. medRxiv 2022.01.20.22269617; doi: https://doi.org/10.1101/2022.01.20.22269617 (Full text)

Chronic Fatigue and Postexertional Malaise in People Living with Long COVID: An Observational Study

Abstract:

Objectives: People living with long COVID describe a high symptom burden, and a more detailed assessment is needed to inform rehabilitation recommendations. The objectives were to use validated questionnaires to measure the severity of fatigue and compare this with normative data and thresholds for clinical relevance in other diseases; measure and describe the impact of postexertional malaise (PEM); and assess symptoms of dysfunctional breathing, self-reported physical activity, and health-related quality of life.

Methods: This was an observational study with a cross-sectional survey design (data collection from February 2021 to April 2021). Eligible participants were adults experiencing persistent symptoms due to COVID-19 that did not predate the confirmed or suspected infection. Questionnaires included the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and the DePaul Symptom Questionnaire-Post-Exertional Malaise.

Results: After data cleaning, 213 participants were included in the analysis. The total FACIT-F score was 18 (SD = 10) (where the score can range from 0 to 52 and a lower score indicates more severe fatigue), and 71.4% were experiencing chronic fatigue. Postexertional symptom exacerbation affected most participants, and 58.7% met the PEM scoring thresholds used in people living with myalgic encephalomyelitis/chronic fatigue syndrome.

Conclusion: Long COVID is characterized by chronic fatigue that is clinically relevant and at least as severe as fatigue in several other clinical conditions. PEM is a significant challenge for this patient group. Because of the potential for setbacks and deteriorated function following overexertion, fatigue and postexertional symptom exacerbation must be monitored and reported in clinical practice and in studies involving interventions for people with long COVID.

Impact: Physical therapists working with people with long COVID should measure and validate the patient’s experience. Postexertional symptom exacerbation must be considered, and rehabilitation needs to be carefully designed based on individual presentation. Beneficial interventions might first ensure symptom stabilization via pacing, a self-management strategy for the activity that helps minimize postexertional malaise.

Source: Twomey R, DeMars J, Franklin K, Culos-Reed SN, Weatherald J, Wrightson JG. Chronic Fatigue and Postexertional Malaise in People Living with Long COVID: An Observational Study. Phys Ther. 2022 Jan 13:pzac005. doi: 10.1093/ptj/pzac005. Epub ahead of print. PMID: 35079817. https://pubmed.ncbi.nlm.nih.gov/35079817/