Category: Overlapping Illnesses

Persistent symptoms after COVID-19 during the first wave are not associated with differential immunity to SARS-CoV-2

Abstract:

Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection – some have proposed that Long Covid may be a consequence of either an excessive or inadequate initial response. We analysed SARS-CoV-2 humoral and cellular immunity in healthcare workers infected during the first wave.

Symptom questionnaires allowed stratification into those with persistent symptoms and those without for comparison. During the period up to 18-weeks post-infection, we observed no difference in antibody responses to spike, RBD or nucleoprotein, virus neutralisation, or T cell responses. Also, there was no difference in the profile of antibody waning.

Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again showed similar SARS-CoV-2 immunity. Thus, quantitative differences in SARS-CoV-2 adaptive immunity during acute infection are unlikely to contribute to Long Covid causality.

Source: Altmann D, Reynolds C, Joy G, et al. Persistent symptoms after COVID-19 during the first wave are not associated with differential immunity to SARS-CoV-2. Research Square; 2022. DOI: 10.21203/rs.3.rs-2324777/v1. https://www.researchsquare.com/article/rs-2324777/v1 (Full text)

Stellate Ganglion Block for Long COVID Symptom Management: A Case Report

Abstract:

Stellate ganglion block (SGB) is gaining increasing acceptance as a treatment modality for various medical conditions. It works by blocking neuronal transmissions which in turn alleviates sympathetically-driven disease processes. Many of the prolonged sequelae of long COVID are thought to be mediated by dysregulation of the autonomic nervous system, and SGB is being investigated as a potential option for symptomatic management of long COVID. This case report demonstrates the efficacy of SGB in a previously healthy patient for the management of long COVID symptoms including fatigue, post-exertional malaise, shortness of breath, and gastrointestinal symptoms.

Source: Khan M H, Kirkpatrick K P, Deng Y, et al. (December 07, 2022) Stellate Ganglion Block for Long COVID Symptom Management: A Case Report. Cureus 14(12): e32295. doi:10.7759/cureus.32295 https://www.cureus.com/articles/127985-stellate-ganglion-block-for-long-covid-symptom-management-a-case-report (Full text)

The bidirectional association between diabetes and long-COVID-19 – A systematic review

Abstract:

Some evidence suggests that diabetes may be a risk factor for the development of post-acute sequelae of COVID-19 (PASC). Recent data also indicate that new-onset diabetes may be a complication of COVID-19. Here, we review the existing evidence.

Following PRISMA guidelines, we conducted a systematic review through August 8, 2022. We included longitudinal studies reporting on the risk of PASC (i.e., sequelae that extend beyond four weeks after initial infection) in people with and without diabetes, and studies reporting on the risk of new-onset diabetes in people with vs without COVID-19 with a minimum of 4-weeks of follow-up. All studies were published in English. Among 5,532 studies screened, 39 were included in the final review.

Among 25 studies reporting on diabetes and PASC, 44 % (n = 11) identified diabetes as a significant risk factor for PASC (increased relative risk ranging from 7 % to 342 %) while 56 % (n = 14) did not. Among 14 studies reporting on new-onset diabetes, 12 (86 %) reported that COVID-19 (vs no COVID) was significantly associated with new-onset diabetes with increased risks ranging from 11 % to 276 %. COVID-19 survivors may be at increased risk for new-onset diabetes, but whether pre-existing diabetes is also a risk factor for PASC remains unclear.

Source: Harding JL, Oviedo SA, Ali MK, Ofotokun I, Gander JC, Patel SA, Magliano DJ, Patzer RE. The bidirectional association between diabetes and long-COVID-19 – A systematic review. Diabetes Res Clin Pract. 2022 Dec 7;195:110202. doi: 10.1016/j.diabres.2022.110202. Epub ahead of print. PMID: 36496030; PMCID: PMC9727969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727969/ (Full text)

Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics

Abstract:

Symptom treatments for Coronavirus disease 2019 (COVID-19) infection and Long COVID are one of the most critical issues of the pandemic era. In light of the lack of standardized medications for treating COVID-19 symptoms, traditional Chinese medicine (TCM) has emerged as a potentially viable strategy based on numerous studies and clinical manifestations. Taiwan Chingguan Yihau (NRICM101), a TCM designed based on a medicinal formula with a long history of almost 500 years, has demonstrated its antiviral properties through clinical studies, yet the pharmacogenomic knowledge for this formula remains unclear. The molecular mechanism of NRICM101 was systematically analyzed by using exploratory bioinformatics and pharmacodynamics (PD) approaches.

Results showed that there were 434 common interactions found between NRICM101 and COVID-19 related genes/proteins. For the network pharmacology of the NRICM101, the 434 common interacting genes/proteins had the highest associations with the interleukin (IL)-17 signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, the tumor necrosis factor (TNF) was found to have the highest association with the 30 most frequently curated NRICM101 chemicals.

Disease analyses also revealed that the most relevant diseases with COVID-19 infections were pathology, followed by cancer, digestive system disease, and cardiovascular disease. The 30 most frequently curated human genes and 2 microRNAs identified in this study could also be used as molecular biomarkers or therapeutic options for COVID-19 treatments.

In addition, dose-response profiles of NRICM101 doses and IL-6 or TNF-α expressions in cell cultures of murine alveolar macrophages were constructed to provide pharmacodynamic (PD) information of NRICM101. The prevalent use of NRICM101 for standardized treatments to attenuate common residual syndromes or chronic sequelae of COVID-19 were also revealed for post-pandemic future.

Source: Singh S, Yang YF. Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics. Int J Mol Sci. 2022 Dec 6;23(23):15385. doi: 10.3390/ijms232315385. PMID: 36499711; PMCID: PMC9740625. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740625/ (Full text)

Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review

Abstract:

Vaccines against SARS-CoV-2 have saved millions of lives and played an important role in containing the COVID-19 pandemic. Vaccination against SARS-CoV-2 is also associated with reduced disease severity and, perhaps, with COVID-19 symptom burden.

In this narrative review, we present, in a clinically relevant question-and-answer manner, the evidence regarding the association between vaccination against SARS-CoV-2 and long COVID-19. We discuss how the mechanism of action of vaccines could interplay with the pathophysiology of post-COVID-19 condition.

Furthermore, we describe how specific factors, such as the number of vaccine doses and the type of SARS-CoV-2 variants, may affect post-COVID-19 condition. We also discuss the role of timing for vaccination in relation to the onset of long COVID-19 symptoms, as it seems to affect the frequency and severity of the condition.

Additionally, we describe the potential modifying effect of age, as well as the association of type and level of immune response with long COVID-19. We also describe how system-specific long COVID-19 sequelae, namely neurocognitive-psychologic symptoms and cardiovascular pathology, could be altered by vaccination.

Last, we address the question of whether seasonal influenza vaccination has a meaningful impact on the frequency of long COVID-19.

Source: Tofarides AG, Christaki E, Milionis H, Nikolopoulos GK. Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review. Life (Basel). 2022 Dec 8;12(12):2057. doi: 10.3390/life12122057. PMID: 36556422. https://www.mdpi.com/2075-1729/12/12/2057 (Full text)

The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis

Abstract:

Background: Although multiple studies have revealed that coronavirus disease 2019 (COVID-19) vaccines can reduce COVID-19-related outcomes, little is known about their impact on post-COVID-19 conditions. We performed a systematic literature review and meta-analysis on the effectiveness of COVID-19 vaccination against post-COVID-19 conditions (ie, long COVID).

Methods: We searched PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to April 27, 2022, for studies evaluating COVID-19 vaccine effectiveness against post-COVID-19 conditions among individuals who received at least 1 dose of Pfizer/BioNTech, Moderna, AstraZeneca, or Janssen vaccine. A post-COVID-19 condition was defined as any symptom that was present 3 or more weeks after having COVID-19. Editorials, commentaries, reviews, study protocols, and studies in the pediatric population were excluded. We calculated the pooled diagnostic odds ratios (DORs) for post-COVID-19 conditions between vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% × (1 – DOR).

Results: In total, 10 studies with 1,600,830 individuals evaluated the effect of vaccination on post-COVID-19 conditions, of which 6 studies were included in the meta-analysis. The pooled DOR for post-COVID-19 conditions among individuals vaccinated with at least 1 dose was 0.708 (95% confidence interval (CI), 0.692-0.725) with an estimated vaccine effectiveness of 29.2% (95% CI, 27.5%-30.8%). The vaccine effectiveness was 35.3% (95% CI, 32.3%-38.1%) among those who received the COVID-19 vaccine before having COVID-19, and 27.4% (95% CI, 25.4%-29.3%) among those who received it after having COVID-19.

Conclusions: COVID-19 vaccination both before and after having COVID-19 significantly decreased post-COVID-19 conditions for the circulating variants during the study period although vaccine effectiveness was low.

Source: Marra AR, Kobayashi T, Suzuki H, Alsuhaibani M, Hasegawa S, Tholany J, Perencevich E, Maezato AM, Ricardo VCV, Salinas JL, Edmond MB, Rizzo LV. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrob Steward Healthc Epidemiol. 2022 Dec 6;2(1):e192. doi: 10.1017/ash.2022.336. PMID: 36505947; PMCID: PMC9726631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726631/ (Full text)

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial

Abstract:

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis.

A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence.

Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03).

The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

Source: Tosato M, Calvani R, Picca A, Ciciarello F, Galluzzo V, Coelho-Júnior HJ, Di Giorgio A, Di Mario C, Gervasoni J, Gremese E, Leone PM, Nesci A, Paglionico AM, Santoliquido A, Santoro L, Santucci L, Tolusso B, Urbani A, Marini F, Marzetti E, Landi F; Gemelli against COVID-19 Post-Acute Care Team. Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial. Nutrients. 2022 Nov 23;14(23):4984. doi: 10.3390/nu14234984. PMID: 36501014; PMCID: PMC9738241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738241/ (Full text)

Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases

Abstract:

Background: This study examined neuropathological findings of patients who died following hospitalization in an intensive care unit with SARS-CoV-2.

Methods: Data originate from 20 decedents who underwent brain autopsy followed by ex-vivo imaging and dissection. Systematic neuropathologic examinations were performed to assess histopathologic changes including cerebrovascular disease and tissue injury, neurodegenerative diseases, and inflammatory response. Cerebrospinal fluid (CSF) and fixed tissues were evaluated for the presence of viral RNA and protein.

Results: The mean age-at-death was 66.2 years (range: 26-97 years) and 14 were male. The patient’s medical history included cardiovascular risk factors or diseases (n = 11, 55%) and dementia (n = 5, 25%). Brain examination revealed a range of acute and chronic pathologies. Acute vascular pathologic changes were common in 16 (80%) subjects and included infarctions (n = 11, 55%) followed by acute hypoxic/ischemic injury (n = 9, 45%) and hemorrhages (n = 7, 35%). These acute pathologic changes were identified in both younger and older groups and those with and without vascular risk factors or diseases. Moderate-to-severe microglial activation were noted in 16 (80%) brains, while moderate-to-severe T lymphocyte accumulation was present in 5 (25%) brains. Encephalitis-like changes included lymphocytic cuffing (n = 6, 30%) and neuronophagia or microglial nodule (most prominent in the brainstem, n = 6, 30%) were also observed. A single brain showed vasculitis-like changes and one other exhibited foci of necrosis with ball-ring hemorrhages reminiscent of acute hemorrhagic leukoencephalopathy changes. Chronic pathologies were identified in only older decedents: 7 brains exhibited neurodegenerative diseases and 8 brains showed vascular disease pathologies. CSF and brain samples did not show evidence of viral RNA or protein.

Conclusions: Acute tissue injuries and microglial activation were the most common abnormalities in COVID-19 brains. Focal evidence of encephalitis-like changes was noted despite the lack of detectable virus. The majority of older subjects showed age-related brain pathologies even in the absence of known neurologic disease. Findings of this study suggest that acute brain injury superimposed on common pre-existing brain disease may put older subjects at higher risk of post-COVID neurologic sequelae.

Source: Agrawal S, Farfel JM, Arfanakis K, Al-Harthi L, Shull T, Teppen TL, Evia AM, Patel MB, Ely EW, Leurgans SE, Bennett DA, Mehta R, Schneider JA. Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases. Acta Neuropathol Commun. 2022 Dec 17;10(1):186. doi: 10.1186/s40478-022-01493-7. PMID: 36528671; PMCID: PMC9758667. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9758667/ (Full text)

ME/CFS and Post-Exertional Malaise among Patients with Long COVID

Abstract:

This study sought to ascertain the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) among a sample of 465 patients with Long COVID. The participants completed three questionnaires: (1) a new questionnaire measuring both the frequency and severity of 38 common symptoms of COVID and Long COVID, (2) a validated short form questionnaire assessing ME/CFS, and (3) a validated questionnaire measuring post-exertional malaise.
The population was predominantly white, female, and living in North America. The mean duration since the onset of COVID-19 symptoms was 70.5 weeks. Among the 465 participants, 58% met a ME/CFS case definition. Of respondents who reported that they had ME/CFS only 70.57% met criteria for ME/CFS and of those who did not report they had ME/CFS, 29.43% nevertheless did meet criteria for the disease: both over-diagnosis and under-diagnosis were evident on self-report. This study supports prior findings that ME/CFS occurs with high prevalence among those who have persistent COVID-19 symptoms.
Source: Jason LA, Dorri JA. ME/CFS and Post-Exertional Malaise among Patients with Long COVID. Neurology International. 2023; 15(1):1-11. https://doi.org/10.3390/neurolint15010001 https://www.mdpi.com/2035-8377/15/1/1 (Full text)