Tag: long covid symptoms

Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study

Abstract:

Background: Gastrointestinal infections represent a risk factor for functional gastrointestinal and somatoform extraintestinal disorders. We investigated the prevalence and relative risk (RR) of gastrointestinal and somatoform symptoms 5 months after SARS-CoV-2 infection compared with a control cohort.

Methods: One hundred and sixty-four SARS-CoV-2 infected patients and 183 controls responded to an online questionnaire about symptoms and signs during the acute phase of the infection and after 4.8 ± 0.3 months. Presence and severity of gastrointestinal symptoms, somatization, anxiety, and depression were recorded with standardized questionnaires. Stool form and presence of irritable bowel syndrome (IBS) were also recorded. Any association between exposure to infection and symptoms was evaluated by calculating crude and adjusted RR values and score differences with 95% confidence intervals (CI).

Key results: Fever, dyspnea, loss of smell/taste/weight, diarrhea, myalgia, arthralgia, and asthenia were reported by more than 40% of patients during the acute phase. Compared with controls, adjusted RRs for loose stools, chronic fatigue, and somatization were increased after infection: 1.88 (95% CI 0.99-3.54), 2.24 (95% CI 1.48-3.37), and 3.62 (95% CI 1.01-6.23), respectively. Gastrointestinal sequelae were greater in patients with diarrhea during the acute phase.

Conclusions & inferences: Mild gastroenterological symptoms persist 5 months after SARS-CoV-2 infection, in particular in patients reporting diarrhea in the acute phase. Infected patients are at increased risk of chronic fatigue and somatoform disorders, thus supporting the hypothesis that both functional gastrointestinal and somatoform disorders may have a common biological origin.

Source: Noviello D, Costantino A, Muscatello A, Bandera A, Consonni D, Vecchi M, Basilisco G. Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study. Neurogastroenterol Motil. 2022 Feb;34(2):e14187. doi: 10.1111/nmo.14187. Epub 2021 Jun 1. PMID: 34060710; PMCID: PMC8209890. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209890/ (Full text)

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients

Abstract:

Long COVID refers to patients with symptoms as fatigue, “brain fog,” pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB-). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7% of participants reported fatigue while 29.3% were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB- one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways.

Source: Santinelli L, Laghi L, Innocenti GP, Pinacchio C, Vassalini P, Celani L, Lazzaro A, Borrazzo C, Marazzato M, Tarsitani L, Koukopoulos AE, Mastroianni CM, d’Ettorre G, Ceccarelli G. Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients. Front Nutr. 2022 Jan 12;8:756177. doi: 10.3389/fnut.2021.756177. PMID: 35096923; PMCID: PMC8790565. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790565/ (Full text)

The Investigation of Pulmonary Abnormalities using Hyperpolarised Xenon Magnetic Resonance Imaging in Patients with Long-COVID

Abstract:

Background: Long-COVID is an umbrella term used to describe ongoing symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is one of the most common and can persist for months after the initial infection. Investigations including Computed Tomography (CT), and physiological measurements (lung function tests) are usually unremarkable. The mechanisms driving breathlessness remain unclear, and this may be hindering the development of effective treatments.

Methods: Eleven non-hospitalised Long-COVID (NHLC, 4 male), 12 post-hospitalised COVID-19 (PHC, 10 male) patients were recruited from a Post-COVID Assessment clinic, and thirteen healthy controls (6 female) were recruited to undergo Hyperpolarized Xenon Magnetic Resonance Imaging (Hp-XeMRI). NHLC and PHC participants underwent contemporaneous CT, Hp-XeMRI, lung function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Statistical analysis included group and pair-wise comparisons between patients and controls, and correlations between patient clinical and imaging data.

Results: NHLC and PHC patients were 287 ± 79 [range 190-437] and 149 ± 68 [range 68-269] days from infection, respectively. All NHLC patients had normal CT scans, and the PHC had normal or near normal CT scans (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively). There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04) but no differences in other measurements of lung function. There were significant differences in RBC:TP mean between volunteers (0.45 ± 0.07, range [0.33-0.55]) and PHC (0.31 ± 0.11, [range 0.16-0.37]) and NHLC (0.35 ± 0.09, [range 0.26-0.58]) patients, but not between NHLC and PHC (p = 0.26).

Conclusion: There are RBC:TP abnormalities in NHLC and PHC patients, with NHLC patients also demonstrating lower TLco than PHC patients despite their having normal CT scans. These abnormalities are present many months after the initial infection.

Summary statement: Hyperpolarized Xenon MRI and TLco demonstrate significantly impaired gas transfer in non-hospitalised long-COVID patients when all other investigations are normal.

Source:  James T. Grist, Guilhem J. Collier, Huw Walters, Mitchell Chen, Gabriele Abu Eid, Aviana Laws, Violet Matthews, Kenneth Jacob, Susan Cross, Alexandra Eves, Marianne Durant, Anthony Mcintyre, Roger Thompson, Rolf F. Schulte, Betty Raman, Peter A. Robbins, Jim M. Wild, Emily Fraser, Fergus Gleeson. The Investigation of Pulmonary Abnormalities using Hyperpolarised Xenon Magnetic Resonance Imaging in Patients with Long-COVID.
medRxiv 2022.02.01.22269999; doi: https://doi.org/10.1101/2022.02.01.22269999

Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort

Abstract:

Background: The burden of long-term symptoms (i.e. long-COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCW), frequency and risk factors for symptoms compatible with long-COVID are assessed.

Methods: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long-COVID (including psychometric scores) were asked and compared between HCW with positive NPS, seropositive HCW without positive NPS (presumable a-/pauci-symptomatic infections), and negative controls. Also, the effect of time since diagnosis and quantitative anti-S was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

Results: Of 3’334 HCW (median 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCW with positive NPS more frequently reported ≥1 symptom compared to controls (73%vs.52%, p<0.001); seropositive HCW without positive NPS did not score higher than controls (58%vs.52%, p=0.13), although impaired taste/olfaction (16%vs.6%, p<0.001) and hair loss (17%vs.10%, p=0.004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

Conclusions: Seropositive HCW without positive NPS are only mildly affected by long-COVID. Exhaustion/burnout is common, even in non-infected HCW. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Source: Strahm C, Seneghini M, Güsewell S, Egger T, Leal O, Brucher A, Lemmenmeier E, Meier Kleeb D, Möller JC, Rieder P, Ruetti M, Rutz R, Schmid HR, Stocker R, Vuichard-Gysin D, Wiggli B, Besold U, Kuster SP, McGeer A, Risch L, Friedl A, Schlegel M, Schmid D, Vernazza P, Kahlert CR, Kohler P. Symptoms compatible with long-COVID in healthcare workers with and without SARS-CoV-2 infection – results of a prospective multicenter cohort. Clin Infect Dis. 2022 Jan 28:ciac054. doi: 10.1093/cid/ciac054. Epub ahead of print. PMID: 35090015. https://pubmed.ncbi.nlm.nih.gov/35090015/  (Full text available as PDF file)

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)