Category: Overlapping Illnesses

Webinar: New Hope for Diagnosing and Treating Post-Infection Illnesses: Lessons Learned from HIV/AIDS

Webinar:

Drs. Steven Deeks and David Hardy (Solve M.E. Medical Advisor) — two long-time researchers, clinicians, and veterans of the battle against HIV/AIDS, discussed how current studies on Long Covid, informed by knowledge gained in other fields, could help develop improved ways to diagnose and treat the broader challenge of post-infection illnesses, such as ME/CFS. In their conversation, Drs. Deeks and Hardy discussed the emerging scientific and medical findings, reflected on their HIV/AIDS experience and the importance of patient engagement in research and advocacy, and discussed the prospects for treatments and therapies.

A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants

Abstract:

A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics.

We find that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We find that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus.

Source: Farley SE, Kyle JE, Leier HC, Bramer LM, Weinstein JB, Bates TA, Lee JY, Metz TO, Schultz C, Tafesse FG. A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants. Nat Commun. 2022 Jun 17;13(1):3487. doi: 10.1038/s41467-022-31097-7. PMID: 35715395; PMCID: PMC9203258. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203258/ (Full text)

Post-acute Sequelae of SARS-CoV-2 Infection: A Neglected Public Health Issue

Introduction:

The COVID-19 pandemic has caused at least 508,827,830 infections and is associated with a 1.2% mortality rate worldwide (). New SARS-CoV-2 variants have driven new waves of the pandemic as a result of their increased transmissibility and ability to evade the immune response (). The post-acute sequelae of SARS-CoV-2 infection (PASC) is an important but underestimated public health issue that can have a long-term impact on pulmonary and multiple extrapulmonary tissues and organs through several potential mechanisms (, ). Recent studies demonstrate that approximately 4–69% of patients (including children, adolescents, adults, and senior) suffer from PASC (–). There is considerable evidence concerning post-acute sequelae that will likely outlast the current pandemic and need to be addressed. This article reviews the clinical sequelae of COVID-19 survivors and provides valuable insights required to fill the gaps in medical knowledge.

Source: Wang Z, Yang L. Post-acute Sequelae of SARS-CoV-2 Infection: A Neglected Public Health Issue. Front Public Health. 2022 Jun 17;10:908757. doi: 10.3389/fpubh.2022.908757. PMID: 35784200; PMCID: PMC9247346. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247346/ (Full text)

Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence

Abstract:

in English, Italian

Objective: The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with “long-COVID”.

Methods: The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2.

Results: 1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021.

Conclusions: The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.

Source: De Luca P, Di Stadio A, Colacurcio V, Marra P, Scarpa A, Ricciardiello F, Cassandro C, Camaioni A, Cassandro E. Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence. Acta Otorhinolaryngol Ital. 2022 Apr;42(Suppl. 1):S87-S93. doi: 10.14639/0392-100X-suppl.1-42-2022-10. PMID: 35763279; PMCID: PMC9137376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137376/ (Full text)

High-density EEG sleep correlates of cognitive and affective impairment at 12-month follow-up after COVID-19

Abstract:

Objective: To disentangle the pathophysiology of cognitive/affective impairment in Coronavirus Disease-2019 (COVID-19), we studied long-term cognitive and affective sequelae and sleep high-density electroencephalography (EEG) at 12-month follow-up in people with a previous hospital admission for acute COVID-19.

Methods: People discharged from an intensive care unit (ICU) and a sub-intensive ward (nonICU) between March and May 2020 were contacted between March and June 2021. Participants underwent cognitive, psychological, and sleep assessment. High-density EEG recording was acquired during a nap. Slow and fast spindles density/amplitude/frequency and source reconstruction in brain gray matter were extracted. The relationship between psychological and cognitive findings was explored with Pearson correlation.

Results: We enrolled 33 participants ( 17 nonICU) and 12 controls. We observed a lower Physical Quality of Life index, higher post-traumatic stress disorder (PTSD) score, and a worse executive function performance in nonICU participants. Higher PTSD and Beck Depression Inventory scores correlated with lower executive performance. The same group showed a reorganization of spindle cortical generators.

Conclusions: Our results show executive and psycho-affective deficits and spindle alterations in COVID-19 survivors – especially in nonICU participants – after 12 months from discharge.

Significance: These findings may be suggestive of a crucial contribution of stress experienced during hospital admission on long-term cognitive functioning.

Source: Rubega M, Ciringione L, Bertuccelli M, Paramento M, Sparacino G, Vianello A, Masiero S, Vallesi A, Formaggio E, Del Felice A. High-density EEG sleep correlates of cognitive and affective impairment at 12-month follow-up after COVID-19. Clin Neurophysiol. 2022 Jun 15;140:126-135. doi: 10.1016/j.clinph.2022.05.017. Epub ahead of print. PMID: 35763985; PMCID: PMC9292469. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292469/ (Full text)

Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records

Abstract:

The frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.

Source: Thompson EJ, Williams DM, Walker AJ, Mitchell RE, Niedzwiedz CL, Yang TC, Huggins CF, Kwong ASF, Silverwood RJ, Di Gessa G, Bowyer RCE, Northstone K, Hou B, Green MJ, Dodgeon B, Doores KJ, Duncan EL, Williams FMK; OpenSAFELY Collaborative, Steptoe A, Porteous DJ, McEachan RRC, Tomlinson L, Goldacre B, Patalay P, Ploubidis GB, Katikireddi SV, Tilling K, Rentsch CT, Timpson NJ, Chaturvedi N, Steves CJ. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records. Nat Commun. 2022 Jun 28;13(1):3528. doi: 10.1038/s41467-022-30836-0. PMID: 35764621; PMCID: PMC9240035.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240035/ (Full text)

COVID fog demystified

Abstract:

Acute mild respiratory SARS-CoV-2 infection can lead to a more chronic cognitive syndrome known as “COVID fog.” New findings from Fernández-Castañeda et al. reveal how glial dysregulation and consequent neural circuit dysfunction may contribute to cognitive impairments in long COVID.

Source: Kao J, Frankland PW. COVID fog demystified. Cell. 2022 Jul 7;185(14):2391-2393. doi: 10.1016/j.cell.2022.06.020. Epub 2022 Jun 15. PMID: 35768007; PMCID: PMC9197953. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197953/ (Full text)

Bridging Knowledge Gaps in the Diagnosis and Management of Neuropsychiatric Sequelae of COVID-19

Abstract:

Importance: Neuropsychiatric symptoms have been reported as a prominent feature of postacute sequelae of COVID-19 (PASC), with common symptoms that include cognitive impairment, sleep difficulties, depression, posttraumatic stress, and substance use disorders. A primary challenge of parsing PASC epidemiology and pathophysiology is the lack of a standard definition of the syndrome, and little is known regarding mechanisms of neuropsychiatric PASC.

Observations: Rates of symptom prevalence vary, but at least 1 PASC neuropsychiatric symptom has been reported in as many as 90% of patients 6 months after COVID-19 hospitalization and in approximately 25% of nonhospitalized adults with COVID-19. Mechanisms of neuropsychiatric sequelae of COVID-19 are still being elucidated. They may include static brain injury accrued during acute COVID-19, neurodegeneration triggered by secondary effects of acute COVID-19, autoimmune mechanisms with chronic inflammation, viral persistence in tissue reservoirs, or reactivation of other latent viruses. Despite rapidly emerging data, many gaps in knowledge persist related to the variable definitions of PASC, lack of standardized phenotyping or biomarkers, variability in virus genotypes, ascertainment biases, and limited accounting for social determinants of health and pandemic-related stressors.

Conclusions and relevance: Growing data support a high prevalence of PASC neuropsychiatric symptoms, but the current literature is heterogeneous with variable assessments of critical epidemiological factors. By enrolling large patient samples and conducting state-of-the-art assessments, the Researching COVID to Enhance Recovery (RECOVER), a multicenter research initiative funded by the National Institutes of Health, will help clarify PASC epidemiology, pathophysiology, and mechanisms of injury, as well as identify targets for therapeutic intervention.

Source: Frontera JA, Simon NM. Bridging Knowledge Gaps in the Diagnosis and Management of Neuropsychiatric Sequelae of COVID-19. JAMA Psychiatry. 2022 Jun 29. doi: 10.1001/jamapsychiatry.2022.1616. Epub ahead of print. PMID: 35767287.  https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2793903 (Full text)

Neurovascular injury with complement activation and inflammation in COVID-19

Abstract:

The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms. In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry.

All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed.

All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia.

Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.

Source: Lee MH, Perl DP, Steiner J, Pasternack N, Li W, Maric D, Safavi F, Horkayne-Szakaly I, Jones R, Stram MN, Moncur JT, Hefti M, Folkerth RD, Nath A. Neurovascular injury with complement activation and inflammation in COVID-19. Brain. 2022 Jul 5:awac151. doi: 10.1093/brain/awac151. Epub ahead of print. PMID: 35788639; PMCID: PMC9278212. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278212/ (Full text)

Microvascular Injury in the Brains of Patients with Covid-19

To the Editor:

We conducted postmortem high-resolution magnetic resonance imaging (magnetic resonance microscopy) of the brains of patients with coronavirus disease 2019 (Covid-19) (median age, 50 years) and histopathological examination that focused on microvascular changes in the olfactory bulb and brain stem. (See the Materials and Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org.) Images were obtained from the brains of 13 patients with the use of an 11.7-Tesla scanner at a resolution of 25 μm for the olfactory bulb and at a resolution of 100 μm for the brain. Abnormalities were seen in the brains of 10 patients.

We examined the brains of patients that showed abnormalities by means of multiplex fluorescence imaging (in 5 patients) and by means of chromogenic immunostaining (in 10 patients). We performed conventional histopathological examination of the brains of 18 patients. Fourteen patients had chronic illnesses, including diabetes and hypertension, and 11 had been found dead or had died suddenly and unexpectedly. Of the 16 patients with available medical histories, 1 had delirium, 5 had mild respiratory symptoms, 4 had acute respiratory distress syndrome, 2 had pulmonary embolism, and the symptoms were not known in 3.

Read the rest of this letter HERE.

Source: Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, Dodd SJ, Koretsky AP, Watts JA, Cheung V, Masliah E, Horkayne-Szakaly I, Jones R, Stram MN, Moncur J, Hefti M, Folkerth RD, Nath A. Microvascular Injury in the Brains of Patients with Covid-19. N Engl J Med. 2021 Feb 4;384(5):481-483. doi: 10.1056/NEJMc2033369. Epub 2020 Dec 30. PMID: 33378608; PMCID: PMC7787217. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787217/ (Full text)