Tag: covid-19

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome

Abstract:

Objective: To describe the clinical data from the first 108 patients seen in the Mayo Clinic post-COVID-19 care clinic (PCOCC).

Methods: After Institutional Review Board approval, we reviewed the charts of the first 108 patients seen between January 19, 2021, and April 29, 2021, in the PCOCC and abstracted from the electronic medical record into a standardized database to facilitate analysis. Patients were grouped into phenotypes by expert review.

Results: Most of the patients seen in our clinic were female (75%; 81/108), and the median age at presentation was 46 years (interquartile range, 37 to 55 years). All had post-acute sequelae of SARS-CoV-2 infection, with 6 clinical phenotypes being identified: fatigue predominant (n=69), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women, and the dyspnea-predominant phenotype was more common in men. Interleukin 6 (IL-6) was elevated in 61% of patients (69% of women; P=.0046), which was more common than elevation in C-reactive protein and erythrocyte sedimentation rate, identified in 17% and 20% of cases, respectively.

Conclusion: In our PCOCC, we observed several distinct clinical phenotypes. Fatigue predominance was the most common presentation and was associated with elevated IL-6 levels and female sex. Dyspnea predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were more likely than erythrocyte sedimentation rate and C-reactive protein to be elevated in patients with post-acute sequelae of SARS-CoV-2 infection.

Source: Ganesh R, Grach SL, Ghosh AK, Bierle DM, Salonen BR, Collins NM, Joshi AY, Boeder ND Jr, Anstine CV, Mueller MR, Wight EC, Croghan IT, Badley AD, Carter RE, Hurt RT. The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome. Mayo Clin Proc. 2022 Feb 5:S0025-6196(21)00888-0. doi: 10.1016/j.mayocp.2021.11.033. Epub ahead of print. PMID: 35135695; PMCID: PMC8817110. https://www.sciencedirect.com/science/article/pii/S0025619621008880 (Full text)

Inappropriate sinus tachycardia in long-COVID and other updates on recent autonomic research

As the COVID-19 pandemic continues to affect hundreds of millions of people worldwide, autonomic complications are being recognized with increasing frequency in both the acute and chronic form of the illness, the latter now designated as post-acute sequelae of SARS-CoV-2 (PASC), colloquially termed long-COVID. Tachycardia is a common symptom of PASC, and some patients may be diagnosed with postural tachycardia syndrome (POTS) or inappropriate sinus tachycardia (IST). While post-COVID POTS has garnered more attention from the scientific and popular press, IST may be equally or more common and has been reported in survivors of the prior SARS coronavirus pandemic [1]. The etiology of IST is unknown; however, the proposed mechanisms overlap with those of POTS, including increased sympathetic and/or reduced cardiovagal activity.

In their recent publication [2], “Inappropriate sinus tachycardia in post-COVID-19 syndrome” Aranyo and colleagues identified 200 consecutive patients with PASC. IST was defined according to consensus criteria as symptomatic sinus rhythm rate ≥ 100 bpm at rest with a mean 24-h heart rate above 90 beats/min in the absence of any acute physiological demand or conditions known to produce sinus tachycardia. All patients underwent a 10-min active stand test to help rule out disorders of orthostatic intolerance, such as POTS and orthostatic hypotension. In addition, patients underwent an echocardiogram, 24-h Holter monitoring, a 6-min walk test (6MWT), and measurements of blood markers of inflammation and myocardial damage, including ferritin and interleukin-6. Heart rate variability (HRV) analysis was performed from the 24-h Holter data, focusing on standard time-domain parameters such as the RR interval, standard deviation of the inter-beat interval (SDNN), and the percentage of adjacent NN intervals that differed from each other by more than 50 ms (PNN50), as well as standard frequency-domain parameters including very low-frequency (VLF; 0.003–0.04 Hz), low-frequency (LF; 0.04–0.15 Hz), and high-frequency (HF; 0.15–0.40 Hz) bands. The HF band and PNN50 are regarded as indicators of the parasympathetic influence on heart rate, whereas the LF and VLF bands have more complex physiology that integrates both the sympathetic and parasympathetic components. Comparison groups included age- and gender-matched PCR-confirmed COVID patients without IST (fully recovered group, N = 19) and age- and gender-matched controls who had no history of SARS-COV-2 disease, as confirmed by negative serology (uninfected group, N = 17).

The authors identified 40 patients with IST from the cohort of 200 patients with PASC yielding an estimated prevalence of 20%. Eighty-five percent of the subjects were women and 83% had a history of mild COVID defined as the presence of symptoms without evidence of viral pneumonia or hypoxia. Most patients reported cardiopulmonary symptoms at the onset of their infection, including palpitations (90%), dyspnea (83%), and chest pain (78%); 53% reported dizziness and 48% anosmia. Compared to fully recovered patients, patients with IST were more likely to report palpitations (90% vs. 5%; p < 0.001), dyspnea (82% vs. 16%; p < 0.001), chest pain (78% vs. 21%; p < 0.001), headache (73% vs. 37%; p = 0.007), dizziness (53% vs. 5%; p = 0.002), diarrhea (53% vs. 16%; p = 0.003), and dermatological alterations (35% vs. 5%; p = 0.009) during the acute phase of SARS-CoV-2 infection. Patients with IST were also more likely to report environmental allergies compared to the fully recovered and uninfected groups (25% vs. 0%; p = 0.01), hinting at a potential mast cell component.

The 6MWT showed that patients with PASC with IST had a significantly reduced exercise capacity, with a 60% reduction in their estimated normal distance. Frequency analysis of heart rate variability revealed that patients with IST had a reduction in VLF, LF, and HF domains compared to controls, with more severe impairment in the parasympathetic-influenced domains. There was no difference in blood inflammatory markers between groups.

Limitations of this work include the small sample sizes of the control groups, as well as the lack of systematic pulmonary evaluations, measurement of markers of physical deconditioning, and systematic autonomic testing. Nonetheless, this study provides the first glimpse of how common IST may be in PASC and adds to the growing body of literature on autonomic dysfunction as a potential mechanism in PASC-related disability. With the Omicron variant currently surging across the globe, PASC-related autonomic complications will, unfortunately, be with us for some time, and clinicians should be familiar with their manifestations and potential treatment options.

Read the rest of this article HERE.

Source: Miglis MG, Larsen N, Muppidi S. Inappropriate sinus tachycardia in long-COVID and other updates on recent autonomic research. Clin Auton Res. 2022 Feb 7. doi: 10.1007/s10286-022-00854-5. Epub ahead of print. PMID: 35129713. https://link.springer.com/article/10.1007/s10286-022-00854-5 (Full text)

Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis

Abstract:

Background: Post-acute COVID-19 Syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity.

Objectives: To estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods.

Data sources: Searches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed.

Study eligibility criteria: Articles in English that reported the prevalence of persistent symptoms among individuals with confirmed SARS-CoV-2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness.

Methods: Random-effect meta-analysis was performed to produce pooled prevalence for each symptom at 4 different follow-up time intervals. Between-studies heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study level variables. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively.

Results: After screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257,348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder and concentration difficulty (32%, 25%, 24%, and 22% respectively at 3-<6 months follow-up), effort intolerance, fatigue, sleep disorder and dyspnea (45%, 36%, 29% and 25% respectively at 6-<9 months follow-up), fatigue (37%) and dyspnea (21%) at 9-<12 months and fatigue, dyspnea, sleep disorder, myalgia (41%, 31%, 30%, and 22% respectively at >12 months follow-up). There was substantial between-studies heterogeneity for all reported symptoms prevalence. Meta-regressions identified statistically significant effect modifiers: world region, male gender, diabetes mellitus, disease severity and overall study quality score. Five of six studies including a comparator group consisting of COVID-19 negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms.

Conclusions: This systematic review found that a large proportion of patients experience PACS 3 to 12 months after recovery from the acute phase of COVD-19. However, available studies of PACS are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptoms definitions and measurements and longer follow-up.

Source: Alkodaymi MS, Omrani OA, Fawzy NA, Shaar BA, Almamlouk R, Riaz M, Obeidat M, Obeidat Y, Gerberi D, Taha RM, Kashour Z, Kashour T, Berbari EF, Alkattan K, Tleyjeh IM. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis. Clin Microbiol Infect. 2022 Feb 3:S1198-743X(22)00038-6. doi: 10.1016/j.cmi.2022.01.014. Epub ahead of print. PMID: 35124265; PMCID: PMC8812092. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812092/ (Full text)

Long COVID Patient Fact Sheet

‘Long COVID’ is the term that is often used to describe these persistent symptoms. You are considered to have ‘Long COVID’ when you are still having symptoms at least 4 weeks after the initial infection. Long COVID may also be referred to by other names such as post-COVID conditions, PASC (post-acute sequelae of COVID-19) or long-haul COVID.

Who Could Develop Long COVID?

Researchers around the world are trying to understand why some people develop Long COVID. People of all ages have been diagnosed with long COVID, including people with no underlying health conditions. Young and otherwise healthy people, and even those with mild infections, can be affected. More research is needed on the wide range of symptoms and why some people have more severe symptoms than others.

Read the full fact sheet as a PDF file HERE.

Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis

Abstract

Importance: Neurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis.

Objective: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults.

Data sources: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1st, 2020 and August 1st, 2021. The systematic review was guided by Preferred Reporting Items for Systematic Review and Meta-Analyses.

Study selection: Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence (NICE) definition of post-COVID-19 syndrome (symptoms that develop or persist ≥3 months after the onset of COVID-19). Additional criteria included the reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19.

Data extraction and synthesis: Two authors independently extracted data on patient characteristics, hospital and/or ICU admission, acute-phase COVID-19 symptoms, length of follow-up, and neurological and neuropsychiatric symptoms.

Main outcome(s) and measure(s): The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. We also compared post-COVID-19 syndrome in hospitalised vs. non-hospitalised patients, with vs. without ICU admission during the acute phase of infection, and with mid-term (3 to 6 months) and long-term (>6 months) follow-up.

Results: Of 1458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were: fatigue (37%, 95% CI: 24%-50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%-34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced frequency of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR: 1.9, 95% CI: 1.4-2.3). Cohorts with >20% of patients admitted to the ICU during acute COVID-19 experienced higher prevalence of fatigue, anxiety, depression, and sleep disturbances than cohorts with <20% of ICU admission.

Conclusions and relevance: Fatigue, cognitive dysfunction (brain fog, memory issues, attention disorder) and sleep disturbances appear to be key features of post-COVID-19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) are common and increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.

Source: Premraj L, Kannapadi NV, Briggs J, Seal SM, Battaglini D, Fanning J, Suen J, Robba C, Fraser J, Cho SM. Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. J Neurol Sci. 2022 Jan 29;434:120162. doi: 10.1016/j.jns.2022.120162. Epub ahead of print. PMID: 35121209; PMCID: PMC8798975. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798975/ (Full text)

Association Between SARS-CoV-2 RNAemia and Postacute Sequelae of COVID-19

Abstract:

Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 83.3% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, worst disease severity, and length of symptoms.

Source: Ram-Mohan N, Kim D, Rogers AJ, Blish CA, Nadeau KC, Blomkalns AL, Yang S. Association Between SARS-CoV-2 RNAemia and Postacute Sequelae of COVID-19. Open Forum Infect Dis. 2021 Dec 25;9(2):ofab646. doi: 10.1093/ofid/ofab646. PMID: 35111870; PMCID: PMC8802799. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802799/ (Full text)

Long-COVID diagnosis: From diagnostic to advanced AI-driven models

Abstract:

SARS-COV 2 is recognized to be responsible for a multi-organ syndrome. In most patients, symptoms are mild. However, in certain subjects, COVID-19 tends to progress more severely. Most of the patients infected with SARS-COV2 fully recovered within some weeks. In a considerable number of patients, like many other viral infections, various long-lasting symptoms have been described, now defined as “long COVID-19 syndrome”. Given the high number of contagious over the world, it is necessary to understand and comprehend this emerging pathology to enable early diagnosis and improve patents outcomes.

In this scenario, AI-based models can be applied in long-COVID-19 patients to assist clinicians and at the same time, to reduce the considerable impact on the care and rehabilitation unit. The purpose of this manuscript is to review different aspects of long-COVID-19 syndrome from clinical presentation to diagnosis, highlighting the considerable impact that AI can have.

Source: Cau R, Faa G, Nardi V, Balestrieri A, Puig J, Suri JS, SanFilippo R, Saba L. Long-COVID diagnosis: From diagnostic to advanced AI-driven models. Eur J Radiol. 2022 Jan 19;148:110164. doi: 10.1016/j.ejrad.2022.110164. Epub ahead of print. PMID: 35114535; PMCID: PMC8791239. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791239/ (Full text)

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 Minocycline Challenge as a Potential First-Line Therapy for Myalgic Encephalomyelitis and Long Covid-19 Syndrome

Abstract:

Chronic fatigue syndrome characterized by severe disabling fatigue, prolonged post-exertional malaise, and unrefreshing sleep markedly reduces the activities of daily living and impairs the quality of life.

Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been postulated as the main cause of chronic fatigue syndrome.

Recently, oral minocycline therapy has been reported to exert favorable therapeutic effects in some patients with ME, especially in the initial stage of the disease, although many patients discontinued treatment in the first few days because of acute adverse effects such as nausea and/or dizziness.

Minocycline appeared to exert a variety of biologic actions against neural inflammation that are independent of their anti-microbial activity, including anti-inflammatory, immunomodulatory, and neuroprotective effects.

In recent years, it has been noted that COVID-19 disease may cause persistent signs and symptoms described as post-COVID syndrome or long COVID, in which the clinical presentation is remarkably similar to those seen in patients with ME.

A wide range of infectious agents have been suggested to trigger the development of ME, and one of such pathogens may be the COVID-19 virus.

Recently, I had a valuable experience of a 22-year-old female patient with a 14-month duration of long COVID who completely recovered from ME-like symptoms after treatment with minocycline. This case suggests that oral minocycline could be an effective first-line therapy for long COVID-19, although a large scale of trial is obviously needed to justify the therapy.

Source: Miwa K. Oral Minocycline Challenge as a Potential First-Line Therapy for Myalgic Encephalomyelitis and Long Covid-19 Syndrome. Ann Clin Med Case Rep. 2022; V8(7): 1-4 https://acmcasereport.com/wp-content/uploads/2022/01/ACMCR-v8-1710.pdf  (Full article available as PDF file)

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)