A comparative study of valaciclovir, valganciclovir, and artesunate efficacy in reactivated HHV-6 and HHV-7 infections associated with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

The study aimed to compare the efficacy of valaciclovir, valganciclovir, and artesunate in treating chronic reactivated HHV-6 and HHV-7 associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). From 255 patients with reactivated HHV-6 and HHV-7 infections (blood leukocyte PCR) in 192 cases, valaciclovir, valganciclovir, or artesunate were administered at a dose of 3,000, 900, and 100 mg per day, respectively, for 3 months (study group). The control group consisted of similar 63 ME/CFS patients not taking any antiviral drugs. The significance of differences was evaluated by Student’s T-test and the non-parametric criterion – the number of Z-signs. Negative PCR results in HHV6 and HHV-7 treated with valaciclovir was achieved in 26% and 23% (first), 34%, and 28% (second), 37% and 34% of cases (third month), respectively (p<0.05; Z<Z0.05 ). The same results with valganciclovir were obtained in 35% and 33% (first), 44% and 39% (second), 48% and 45% (third month), but with artesunate – in 44% and 41% (first), 57% and 53% (second), 68% and 63% of cases (third month), respectively (p<0.05; Z<Z0.05 ). Artesunate is more effective than valganciclovir and valacyclovir in ME/CFS patients with reactivated HHV-6 and HHV-7 infections.

Source: Maltsev D. A comparative study of valaciclovir, valganciclovir, and artesunate efficacy in reactivated HHV-6 and HHV-7 infections associated with chronic fatigue syndrome/myalgic encephalomyelitis. Microbiol Immunol. 2022 Jan 31. doi: 10.1111/1348-0421.12966. Epub ahead of print. PMID: 35102619. https://pubmed.ncbi.nlm.nih.gov/35102619/

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome

Abstract:

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which – combined with age, history of asthma bronchiale, and five symptoms during primary infection – is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.

Source: Cervia C, Zurbuchen Y, Taeschler P, Ballouz T, Menges D, Hasler S, Adamo S, Raeber ME, Bächli E, Rudiger A, Stüssi-Helbling M, Huber LC, Nilsson J, Held U, Puhan MA, Boyman O. Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome. Nat Commun. 2022 Jan 25;13(1):446. doi: 10.1038/s41467-021-27797-1. PMID: 35078982. https://www.nature.com/articles/s41467-021-27797-1 (Full text)

Long covid in children and adolescents

Editorial:

Risk appears low, but many questions remain

Symptoms involving almost every organ system have been reported after SARS-CoV-2 infection.123 Estimates of the prevalence of long covid (also called post-covid-19 condition, post-acute sequelae of covid-19, or chronic covid syndrome) vary considerably, partly because of confusion around the definition. The term long covid encompasses a broad range of symptoms, including objective complications of covid-19 (pulmonary fibrosis, myocardial dysfunction), mental health conditions, and more subjective, non-specific symptoms resembling those seen in post-viral chronic fatigue syndrome (myalgic encephalomyelitis). Most studies to date have substantial limitations, including small cohorts, absence of control groups, non-standardised capture of symptoms, lack of correction for pre-existing medical conditions, participant reported infection, and variation in follow-up, as well as selection, non-response, misclassification, and recall biases.4

In children and adolescents, acute covid-19 is less severe than in adults.56 Concern among many parents has therefore focused more on the potential long term effects of SARS-CoV-2 infection. Unfortunately, fewer data are available on long covid in young people compared with adults.7 The widely quoted one in seven frequency in children is based on a study with a 13% response rate.78

The linked study by Magnusson and colleagues (doi:10.1136/bmj-2021-066809) used nationwide register data from Norway to estimate the impact of covid-19 on long term healthcare use among 1.3 million children and adolescents.9 The authors identified a short term increase in primary (but not specialist) care use after covid-19 in all the studied age groups. This increase was related to respiratory and general or non-specific conditions, mostly in the four weeks after infection. The increase in primary care use persisted for up to six months among children aged 1-5 years. Notably, covid-19 in children had limited overall impact on healthcare services.

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Source: Petra Zimmermann. Long covid in children and adolescents. BMJ 2022; 376 doi: https://doi.org/10.1136/bmj.o143 (Published 20 January 2022) https://www.bmj.com/content/376/bmj.o143.full (Full article)

Covid-19: How Europe is approaching long covid

Maarte Preller leads a Facebook group for patients with long covid in Austria. It has nearly 1500 members so far. In September, Preller, and others like her across Europe, established a new network of patient associations, formed partly through social media websites, called Long Covid Europe. The group is demanding better research and treatment for the tangle of ongoing symptoms that afflict many people who have had covid-19.

A patchwork of small studies has given some indication of what long covid on the continent is like. In a study of 130 cases, 40% of patients reported “persistent fatigue” 60 days after their first symptoms, while 30% reported breathlessness. Another, of 143 patients in Italy, revealed 55% had three or more symptoms 60 days after they were discharged from hospital.1

A preprint posted in January 2022 of an ongoing study of 70 000 Norwegian patients listed altered smell or taste, poor memory, fatigue, and shortness of breath as common symptoms in the country’s first wave (in early 2021), while those infected from autumn 2021 onwards tended to mention muscle and joint pain more. The data suggest that symptoms were experienced for 11-12 months after infection in the first wave and for one to two months in the second.2

A World Health Organization policy brief published earlier this year found that surveillance of long covid was not happening routinely in European countries.1 There are few specialist clinics for the condition—access to such a service largely depends on where you live—and in many countries action seems to be limited to guidance and monitoring.

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Source: Baraniuk C. Covid-19: How Europe is approaching long covid. BMJ. 2022 Jan 20;376:o158. doi: 10.1136/bmj.o158. PMID: 35058230. https://www.bmj.com/content/376/bmj.o158.full (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)

Trigger point injections and dry needling can be effective in treating long COVID syndrome-related myalgia: a case report

Abstract:

Introduction: Myofascial pain is a complex health condition that affects the majority of the general population. Myalgia has been recognized as a symptom of long COVID syndrome. The treatment for long COVID syndrome-related myalgia lacks research. Dry needling is a technique that involves the insertion of a needle into the tissue of, or overlaying, a pain point. Wet needling is the addition of an injection of an analgesic substance such as lidocaine while performing needling. Both dry and wet needling have are practiced as treatment modalities for myofascial pain. Limited literature exists to define long COVID syndrome-related myalgia and its relation to myofascial pain, or to examine the utility of needling techniques for this pain. We report a case of dry and wet needling as effective treatments for long COVID-related myofascial pain.

Case presentation: A 59-year-old, previously healthy Hispanic male with no comorbid conditions was diagnosed with COVID-19 pneumonia. The patient suffered moderate disease without hypoxia and was never hospitalized. Three months later, the patient continued to suffer from symptoms such as exertional dyspnea, “brain fog,” and myalgia. An extensive multisystem workup revealed normal cardiac, pulmonary, and end organ functions. The patient was then diagnosed with long COVID syndrome. The nature and chronicity of the patient’s myalgia meet the criteria for myofascial pain. Both wet and dry needling were used to treat the patient’s myofascial pain, with good short- and long-term therapeutic effects.

Conclusions: COVID-19 infection has been shown to exacerbate preexisting myofascial pain syndrome. Our case report indicates that long COVID syndrome-related myalgia is likely a form of new-onset myofascial pain. Additionally, both wet and dry needling can be utilized as an effective treatment modality for this pain syndrome, with short- and long-term benefits.

Source: Zha M, Chaffee K, Alsarraj J. Trigger point injections and dry needling can be effective in treating long COVID syndrome-related myalgia: a case report. J Med Case Rep. 2022 Jan 17;16(1):31. doi: 10.1186/s13256-021-03239-w. PMID: 35039086; PMCID: PMC8763132. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763132/ (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)
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