Tag: long Covid

The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling

Abstract:

Background: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response.

Methods: We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients’ hospitalization time.

Findings: The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19.

Interpretation: Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID.

Source: Ackermann M, Kamp JC, Werlein C, Walsh CL, Stark H, Prade V, Surabattula R, Wagner WL, Disney C, Bodey AJ, Illig T, Leeming DJ, Karsdal MA, Tzankov A, Boor P, Kühnel MP, Länger FP, Verleden SE, Kvasnicka HM, Kreipe HH, Haverich A, Black SM, Walch A, Tafforeau P, Lee PD, Hoeper MM, Welte T, Seeliger B, David S, Schuppan D, Mentzer SJ, Jonigk DD. The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling. EBioMedicine. 2022 Nov;85:104296. doi: 10.1016/j.ebiom.2022.104296. Epub 2022 Oct 4. PMID: 36206625; PMCID: PMC9535314. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9535314/ (Full text)

Trajectory of Gastrointestinal Symptoms in Previously Hospitalized COVID-19 Survivors: The Long COVID Experience Multicenter Study

Abstract:

This multicenter cohort study used Sankey plots and exponential bar plots to visualize the fluctuating evolution and the trajectory of gastrointestinal symptoms in previously hospitalized COVID-19 survivors during the first 18 months after acute SARS-CoV-2 infection. A total of 1266 previously hospitalized COVID-19 survivors were assessed at four points: hospital admission (T0), at 8.4 months (T1), at 13.2 months (T2), and at 18.3 months (T3) after hospitalization.
Participants were asked about their overall gastrointestinal symptoms and particularly diarrhea. Clinical and hospitalization data were collected from hospital medical records. The prevalence of overall gastrointestinal post-COVID symptomatology was 6.3% (n = 80) at T1, 3.99% (n = 50) at T2 and 2.39% (n = 32) at T3. The prevalence of diarrhea decreased from 10.69% (n = 135) at hospital admission (T0), to 2.55% (n = 32) at T1, to 1.04% (n = 14) at T2, and to 0.64% (n = 8) at T3. The Sankey plots revealed that just 20 (1.59%) and 4 (0.32%) patients exhibited overall gastrointestinal post-COVID symptoms or diarrhea, respectively, throughout the whole follow-up period.
The recovery fitted exponential curves revealed a decreasing prevalence trend, showing that diarrhea and gastrointestinal symptoms recover during the first two or three years after COVID-19 in previously hospitalized COVID-19 survivors. The regression models did not reveal any symptoms to be associated with the presence of gastrointestinal post-COVID symptomatology or post-COVID diarrhea at hospital admission or at T1. The use of Sankey plots revealed the fluctuating evolution of gastrointestinal post-COVID symptoms during the first two years after infection. In addition, exponential bar plots revealed the decreased prevalence of gastrointestinal post-COVID symptomatology during the first three years after infection.
Source: Fernández-de-las-Peñas C, Torres-Macho J, Guijarro C, Martín-Guerrero JD, Pellicer-Valero OJ, Plaza-Manzano G. Trajectory of Gastrointestinal Symptoms in Previously Hospitalized COVID-19 Survivors: The Long COVID Experience Multicenter Study. Viruses. 2023; 15(5):1134. https://doi.org/10.3390/v15051134 https://www.mdpi.com/1999-4915/15/5/1134 (Full text)

Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response

Abstract:

Several millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis.

Both convalescent asymptomatic and PASC cases are characterised by higher CD8+ T cell percentages, however, the proportion of blood CD8+ T cells expressing the mucosal homing receptor β7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease.  Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC.

In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8+β7Integrin+ T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.

Source: Santa Cruz A, Mendes-Frias A, Azarias-da-Silva M, André S, Oliveira AI, Pires O, Mendes M, Oliveira B, Braga M, Lopes JR, Domingues R, Costa R, Silva LN, Matos AR, Ângela C, Costa P, Carvalho A, Capela C, Pedrosa J, Castro AG, Estaquier J, Silvestre R. Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response. Nat Commun. 2023 Mar 30;14(1):1772. doi: 10.1038/s41467-023-37368-1. PMID: 36997530; PMCID: PMC10061413. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10061413/ (Full text)

An Exercise Immune Fitness test to unravel mechanisms of post-acute sequelae of COVID-19

Abstract:

The Post-Acute Sequelae of COVID-19 (PASC) Syndrome is a debilitating syndrome with onset three months post COVID-19 infection, marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnea that is clinically relevant and is at least as severe as fatigue in several other clinical conditions, including cancer. The onset, progression, and symptom profile of PASC patients have considerable overlap with Myalgic-Encephalopathy/Chronic Fatigue Syndrome (ME/CFS).

In people with ME/CFS, exercise (and other types of exertion) can cause serious setbacks and deterioration in function. Post-exertional malaise (PEM) appears to be a common and a significant challenge for the majority of this patient group. Of the nearly 24 million adults in the U.S. who currently have long COVID, more than 80% are having some trouble carrying out daily activities. Mechanisms of PACS remain poorly understood.

While multi-omic information gathered at the time of acute COVID-19 onset may help predict long COVID outcomes, we here propose to test the hypothesis that additional molecular immunological information collected during standardized exercise-testing for cardio-respiratory fitness after recovery from acute COVID-19 can be used to improve the understanding of mechanisms of PASC.

Source: Deng MC. An Exercise Immune Fitness test to unravel mechanisms of post-acute sequelae of COVID-19. Expert Rev Clin Immunol. 2023 May 16. doi: 10.1080/1744666X.2023.2214364. Epub ahead of print. PMID: 37190994. https://www.tandfonline.com/doi/full/10.1080/1744666X.2023.2214364 (Full text)

Long COVID in Children and Youth After Infection or Reinfection with the Omicron Variant: A Prospective Observational Study

Abstract:

To describe the prevalence of long COVID in children infected for the first time (n=332) or reinfected (n=243) with Omicron variant SARS-CoV-2, compared with test-negative children (n=311). 12-16% infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first-positive and reinfection (pchi-square=0.17).

Source: Pinto Pereira SM, Mensah A, Nugawela MD, Stephenson T, Ladhani SN, Dalrymple E, Dudley J, McOwat K, Simmons R, Heyman I, Segal T, Semple MG, Xu L, Shafran R; CLoCk Consortium. Long COVID in Children and Youth After Infection or Reinfection with the Omicron Variant: A Prospective Observational Study. J Pediatr. 2023 May 10:113463. doi: 10.1016/j.jpeds.2023.113463. Epub ahead of print. PMID: 37172813; PMCID: PMC10171900. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171900/ (Full text)

Corona With Lyme: A Long COVID Case Study

Abstract:

The longevity of the coronavirus disease 2019 (COVID-19) pandemic has necessitated continued discussion about the long-term impacts of SARS-CoV-2 infection. Many who develop an acute COVID-19 infection will later face a constellation of enduring symptoms of varying severity, otherwise known as long COVID. As the pandemic reaches its inevitable endemicity, the long COVID patient population will undoubtedly grow and require improved recognition and management. The case presented describes the three-year arc of a previously healthy 26-year-old female medical student from initial infection and induction of long COVID symptomology to near-total remission of the disease. In doing so, the course of this unique post-viral illness and the trials and errors of myriad treatment options will be chronologized, thereby contributing to the continued demand for understanding this mystifying disease.

Source: Thor DC, Suarez S. Corona With Lyme: A Long COVID Case Study. Cureus. 2023 Mar 24;15(3):e36624. doi: 10.7759/cureus.36624. PMID: 37155451; PMCID: PMC10122830. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122830/ (Full text)

COVID-19: Post-recovery Manifestations

Abstract:

Background Post-COVID-19 syndrome, also known as long COVID, is a disorder that has many characteristics, one of which is chronic fatigue following acute infection with the SARS-CoV-2 virus.

Methodology We distributed a web-based survey among patients diagnosed with COVID-19 across the world and collected 190 responses regarding their demographics, histories, COVID-19 infection courses, and common symptoms.

Results We found that about 85.3% of the patients experienced some form of symptom following recovery from the infection. Among the reported symptoms, 59% of patients experienced fatigue or lethargy, 48.9% reported decreased stamina, 32.6% reported shortness of breath, 16.8% had a persistent cough, and 23.7% experienced anxiety following recovery from COVID-19.

Conclusions Reported symptoms closely resembled myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a deeper biochemical understanding of ME/CFS is required to confirm causation.

Source: Shaikh S, Siddiqi Z, Ukachukwu C, Mehkari Z, Khan S, Pamurthy K, Jahan F, Brown A. COVID-19: Post-recovery Manifestations. Cureus. 2023 Mar 29;15(3):e36886. doi: 10.7759/cureus.36886. PMID: 37128534; PMCID: PMC10147564. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147564/ (Full text)

Long COVID: Where Are We in 2023?

Introduction:

The term “COVID Long-Hauler” or “Long-Haul COVID” was first created by patients within few months of the onset of the pandemic., The first publication of persistent symptoms following acute COVID-19 was from Italy in July 2020, where-in, 143 hospitalized patients with acute COVID-19 between April and May 2020, who eventually tested negative by polymerase chain reaction (PCR), were followed for two months as out-patient and 87.4% had at least one persistent symptom. The database study from the United States (U.S.) Department of Veterans Affairs (VA) was the first largest study to show that beyond a month of illness, there existed a higher risk for death and healthcare utilization because of a variety of incident respiratory, cardiovascular, neurological, musculoskeletal, gastrointestinal and metabolic disorders. Subsequently, multiple other observational studies have been published.– The systematic reviews that followed, were limited by the low quality of such studies, lack of standardized definition and representative biologic markers for the different organ systems involved as a part of this syndrome.

Source: Regunath H, Goldstein NM, Guntur VP. Long COVID: Where Are We in 2023? Mo Med. 2023 Mar-Apr;120(2):102-105. PMID: 37091941; PMCID: PMC10121126. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121126/ (Full text)

Lung perfusion assessment in children with long-COVID: A pilot study

Abstract:

Background: There is increasing evidence that chronic endotheliopathy can play a role in patients with Post-Covid Condition (PCC, or Long Covid) by affecting peripheral vascularization. This pilot study aimed at assessing lung perfusion in children with Long-COVID with 99m Tc-MAA SPECT/CT.

Materials and methods: lung 99m Tc-MAA SPECT/CT was performed in children with Long-COVID and a pathological cardiopulmonary exercise testing (CPET). Intravenous injections were performed on patients in the supine position immediately before the planar scan according to the EANM guidelines for lung scintigraphy in children, followed by lung SPECT/CT acquisition. Reconstructed studies were visually analyzed.

Results: Clinical and biochemical data were collected during acute infection and follow-up in 14 children (6 females, mean age: 12.6 years) fulfilling Long-COVID diagnostic criteria and complaining of chronic fatigue and postexertional malaise after mild efforts, documented by CPET. Imaging results were compared with clinical scenarios during acute infection and follow-up. Six out of 14 (42.8%) children showed perfusion defects on 99m Tc-MAA SPECT/CT scan, without morphological alterations on coregistered CT.

Conclusions: This pilot investigation confirmed previous data suggesting that a small subgroup of children can develop lung perfusion defects after severe acute respiratory syndrome coronavirus 2 infection. Larger cohort studies are needed to confirm these preliminary results, providing also a better understanding of which children may deserve this test and how to manage those with lung perfusion defects.

Source: Pizzuto DA, Buonsenso D, Morello R, De Rose C, Valentini P, Fragano A, Baldi F, Di Giuda D. Lung perfusion assessment in children with long-COVID: A pilot study. Pediatr Pulmonol. 2023 Apr 25. doi: 10.1002/ppul.26432. Epub ahead of print. PMID: 37097045. https://onlinelibrary.wiley.com/doi/10.1002/ppul.26432 (Full text)

Long COVID and especially headache syndromes

Abstract:

Purpose of review: This is an expert overview on recent literature about the complex relationship between coronavirus disease 2019 (COVID-19) and headache.

Recent findings: Long COVID is a clinical syndrome characterized by the presence of persistent symptoms following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Headache is one of the most common symptoms and is described most often as throbbing pain, associated with photo and phonofobia and worsening with physical exercise. In acute COVID-19, headache is usually described as moderate or severe, diffuse and oppressive although sometimes it has been described with a migraine-like phenotype, especially in patients with a previous history of migraine.

Headache intensity during acute phase seems to be the most important predictor of duration of headache over time. Some COVID-19 cases can be associated with cerebrovascular complications, and red flags of secondary headaches (e.g. new worsening or unresponsive headache, or new onset of neurological focal signs) should be urgently investigated with imaging. Treatment goals are the reduction of number and intensity of headache crises, and the prevention of chronic forms.

Summary: This review can help clinicians to approach patients with headache and infection from SARS-CoV-2, with particular attention to persistent headache in long COVID.

Source: Tana C, Giamberardino MA, Martelletti P. Long COVID and especially headache syndromes. Curr Opin Neurol. 2023 Jun 1;36(3):168-174. doi: 10.1097/WCO.0000000000001153. Epub 2023 Apr 4. PMID: 37078648. https://pubmed.ncbi.nlm.nih.gov/37078648/