Tag: 2022

Pulmonary Dysfunction after Pediatric COVID-19

Abstract:

Background: Long COVID occurs in lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field MRI may identify persistent pulmonary manifestations after SARS-CoV-2 infection.

Purpose: To characterize both morphologic and functional changes of lung parenchyma on low-field MRI in children and adolescents with post COVID-19 compared with healthy controls.

Materials and Methods: Between August and December 2021, a cross-sectional, prospective clinical trial using low-field MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes on MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive RT-PCR test and serological parameters were compared with imaging results. Nonparametric tests for pairwise and corrected tests for groupwise comparisons were applied to assess differences in healthy controls, recovered participants and with long COVID.

Results: A total of 54 participants post COVID-19 infection (mean age, 11 years ±3 [SD], 56 males) and 9 healthy controls (mean age, 10 years ±3 [SD], 70 males) were included: 29 (54%) in the COVID-19 group had recovered from infection and 25 (46%) were classified as having long COVID on the day of enrollment. Morphologic abnormality was identified in one recovered participant. Both ventilated and perfused lung parenchyma (V/Q match) was reduced from 81±6.1% in healthy controls to 62±19% (P =.006) in the recovered group and 60±20% (P=.003) in the long COVID group. V/Q match was lower in post COVID patients with infection less than 180 days (63±20%, P=.03), 180 to 360 days (63±18%, P=0.03) and 360 days ago (41±12%, P<.001) as compared with the never-infected healthy controls (81±6.1%).

Conclusion: Low-field MRI showed persistent pulmonary dysfunction in both children and adolescents recovered from COVID-19 and with long COVID.

ClinicalTrials.gov: NCT04990531

Source: Heiss R, Tan L, Schmidt S, Regensburger AP, Ewert F, Mammadova D, Buehler A, Vogel-Claussen J, Voskrebenzev A, Rauh M, Rompel O, Nagel AM, Lévy S, Bickelhaupt S, May MS, Uder M, Metzler M, Trollmann R, Woelfle J, Wagner AL, Knieling F. Pulmonary Dysfunction after Pediatric COVID-19. Radiology. 2022 Sep 20:221250. doi: 10.1148/radiol.221250. Epub ahead of print. PMID: 36125379.

Long-term neurologic outcomes of COVID-19

Abstract:

The neurologic manifestations of acute COVID-19 are well characterized, but a comprehensive evaluation of postacute neurologic sequelae at 1 year has not been undertaken. Here we use the national healthcare databases of the US Department of Veterans Affairs to build a cohort of 154,068 individuals with COVID-19, 5,638,795 contemporary controls and 5,859,621 historical controls; we use inverse probability weighting to balance the cohorts, and estimate risks and burdens of incident neurologic disorders at 12 months following acute SARS-CoV-2 infection.

Our results show that in the postacute phase of COVID-19, there was increased risk of an array of incident neurologic sequelae including ischemic and hemorrhagic stroke, cognition and memory disorders, peripheral nervous system disorders, episodic disorders (for example, migraine and seizures), extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain–Barré syndrome, and encephalitis or encephalopathy.

We estimated that the hazard ratio of any neurologic sequela was 1.42 (95% confidence intervals 1.38, 1.47) and burden 70.69 (95% confidence intervals 63.54, 78.01) per 1,000 persons at 12 months. The risks and burdens were elevated even in people who did not require hospitalization during acute COVID-19. Limitations include a cohort comprising mostly White males. Taken together, our results provide evidence of increased risk of long-term neurologic disorders in people who had COVID-19.

Source: Xu, E., Xie, Y. & Al-Aly, Z. Long-term neurologic outcomes of COVID-19. Nat Med (2022). https://doi.org/10.1038/s41591-022-02001-z https://www.nature.com/articles/s41591-022-02001-z (Full text)

Long covid: protesters outside the White House demand better care

Protesters took to the pavement outside the White House on 19 September to demand a better deal for people affected by long covid, complaining that the Biden administration’s plans fell short on action and funding.

“The pandemic is over,” President Joe Biden declared the night before in a pre-recorded interview which aired on the news magazine 60 Minutes. “We still have a problem with covid,” he said. “We’re still doing a lot of work on it but the pandemic is over. If you notice, no one’s wearing masks. Everybody seems to be in pretty good shape. And, so, I think it’s changing.”

But the scene outside the presidential mansion the next day belied that message. Wearing black masks and red shirts, protesters called for research, medical treatment, and social services for those with long covid. Around half would qualify for a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome. The protest was organised by #MEAction, an international network of patient advocates.

“I went undiagnosed for 15 years, because doctors are not educated about the condition,” Jennifer Nish told The BMJ. Nish, from Lubbock, Texas, said that she was inspired to help organise the protest to raise awareness. “I don’t want anyone to go through what I had to go through,” she said and called on “the White House to treat this like the emergency that it is.”

Read the rest of this article HERE.

Source: Roehr B. Long covid: protesters outside the White House demand better care BMJ 2022; 378 :o2266 doi:10.1136/bmj.o2266  https://www.bmj.com/content/378/bmj.o2266 (Full text)

How “long covid” is shedding light on postviral syndromes

Long covid really shouldn’t have been a surprise, says Vett Lloyd, a biologist at Mount Allison University in Sackville, Canada. “When the pandemic started, the general assumption was that there were two possible outcomes to an infection—you’d either get better or die,” she says.

But there’s a possible third outcome. It’s long been known that a number of disease causing pathogens—some viral and some bacterial—are associated with ongoing post-infection symptoms in a significant minority of patients.

“There was no real reason to think SARS-CoV-2 should be any different than the original SARS, which also caused post-infection syndromes,” says Lloyd. She is one of many researchers who hope that the attention and funding directed towards long covid will help to shed light on how and why other infections can lead to persistent and sometimes debilitating symptoms.

Read the rest of this article HERE.

Source: Owens B. How “long covid” is shedding light on postviral syndromes BMJ 2022; 378 :o2188 doi:10.1136/bmj.o2188  https://www.bmj.com/content/378/bmj.o2188 (Full text)

Unpaid carers are the missing piece in treatment guidelines and research priorities for ME/CFS

Dear Editor,

The recent publication of a new NICE Guideline1 , an All-Party Parliamentary Group Report (APPG)2, and new Research Priorities3 heralds a dramatic shift in approaches and attitudes to Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) in the UK. Largely ignored in all three publications, however, are unpaid carers (known outside the UK as family carers or caregivers). The vast majority of people with ME/CFS rely on their families for care and many of those families have been the driving force behind the changes to research and treatment
that are now unfolding.

There has been limited research on unpaid care in the specific context of ME/CFS, but the few existing studies clearly show that the usual toll of caring for a sick or disabled family member is compounded by the historic prejudice surrounding ME/CFS and the absence of evidence-based treatments.g.4-7.

While we applaud the commitment of NICE, the APPG, and the Priority Setting Partnership, it may still be decades before biomedical breakthroughs are made or translated into effective, widely available treatments for ME/CFS8. In the meantime, families will continue to provide the majority of
care for people with ME/CFS and bear the physical, psychological, and economic scars of doing so.

The new NICE guideline does recommend support for carers, but the supports it recommends are generic. They will do little to address the unique needs of ME/CFS carers or their systemic mistreatment by health and social care professionals. A change in the UK’s approach to ME/CFS is long overdue, but without a focus on unpaid carers the puzzle will always be missing a piece. The wellbeing of carers must also be a priority in ME/CFS
research and effective strategies must be developed to address their needs, and recognise and respect their expertise, in clinical practice and social care.

Kind regards,

Dr Siobhan O’Dwyer, University of Exeter Medical School
Ms Sarah Boothby, Former Carer
Dr Georgia Smith, University of Exeter Medical School
Dr Lucy Biddle, Bristol Medical School
Dr Nina Muirhead, Buckinghamshire NHS Trust
Dr Sharmila Khot, Cardiff and Vale University Health Board

Source: O’Dwyer S, Boothby S, Smith G, Biddle L, Muirhead N, Khot S. Unpaid carers are the missing piece in treatment guidelines and research priorities for ME/CFS. BMJ. 2022 Jul 14;378:o1691. doi: 10.1136/bmj.o1691. PMID: 35835467.  https://ore.exeter.ac.uk/repository/bitstream/handle/10871/130699/BMJ_Letter_ODwyer.pdf?sequence=3 (Text available as PDF file)

Higher rates of long covid symptoms in patients with mild covid-19

Abstract:

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has affected over 61 million U.S. citizens, and up to 30-80% of COVID-19 survivors may go on to develop post-acute sequelae of SARS-CoV-2 (PASC). These sequelae can be debilitating and often impair quality of life and daily function. Although it has been suggested that severity of acute COVID-19 infection is directly related to PASC development, this association remains unclear.

METHODS: This prospective cohort study was conducted through consecutive recruitment of confirmed and probable COVID-19 patients with persistent symptoms lasting ≥3 weeks from disease onset or positive SARS-CoV-2 test from academic PASC clinics at Emory University and Grady Memorial Hospital in Atlanta, GA during January-December 2021. Sociodemographic, comorbidity, and acute COVID-19 data were collected. Severe acute COVID- 19 was defined as requiring hospitalization, and critical acute COVID-19 required intensive care. New or worsening symptoms persisting ≥3 weeks from COVID-19 onset were collected using a standardized review of systems, and confirmed by clinician interview. Differences in PASC symptom type were assessed by calculating risk ratios (RR) and 95% confidence intervals (CI) using the Taylor series, and difference in PASC duration was assessed using student’s t-test. Two-tailed p-values ≤0.05 were considered significant.

RESULTS: Of 269 enrollees, median age was 52 years (range 18-93) and there were more women (74%) than men (26%). There were 152 (57%) African American, 76 (28%) White, and 21 (8%) Hispanic. Among PASC patients, the most common symptoms were dyspnea (68%), fatigue (63%), brain fog (48%), dizziness (27%), chest pain (25%), cough (23%) and headache (23%) with a median PASC duration of 132 days (range 21-523). Acute COVID-19 severity was asymptomatic in one participant, mild in 149 (55%), severe in 95 (35%), and critical in 23 (9%). Asymptomatic- mild acute COVID-19 patients had more persistent dyspnea (RR 1.33, 95%, CI 1.09- 1.61), fatigue (RR 1.53, 95%CI 1.22-1.91), brain fog (RR 2.00, 95%CI 1.44-2.67), dizziness (RR 2.03, 95%CI 1.27-3.25), and headache (RR 2.07, 95%CI 1.22-3.48) compared with severe-critical acute disease, who had a non-significant trend towards more cough and chest pain. Asymptomatic-mild participants were further from incident infection (153 days) compared to severe-critical participants (110 days) (p=0.04).

CONCLUSIONS: Contrary to previous observations, COVID-19 survivors who experienced asymptomatic-mild infections may develop higher rates of prevalent PASC symptoms compared to those with severe- critical antecedent infections. These findings are not attributable to PASC duration, as longer PASC duration has been previously associated with fewer symptoms. To ensure early identification and linkage to specialized care, clinicians should be aware of PASC in patients with antecedent asymptomatic-mild acute COVID-19 infections.

Source: Walker, T.; Truong, A.; Summers, A.; Dixit, A.; Goldstein, F.; Hajjar, I.; Echols, M.; Cook, S.; Lee, E.; Tekwani, S.; Carroll, K.; Sanz, I.; Lee, E. H.; Han, J. Higher rates of long covid symptoms in patients with mild covid-19. Journal of General Internal Medicine ; 37:S280, 2022. Article in English | EMBASE | ID: covidwho-1995854 https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1995854?lang=en

Long COVID in children and adolescents

Abstract:

Purpose of review: Although acute COVID-19 has been milder in children and young people compared with adults, there is a concern that they may suffer persistent symptoms. There is a need to define the clinical phenotype, determine those most at risk, the natural course of the condition and evaluate preventive and therapeutic strategies for both mental health and physical symptoms.

Recent findings: More recent studies with control groups reported a lower prevalence of persistent symptoms in children and young people exposed to SARS-CoV-2. A systematic review and meta-analysis found that the frequency of the majority of reported persistent symptoms is similar in SARS-CoV-2 positive cases and controls. Children and young people infected with SARS-COV-2 had small but significant increases in persisting cognitive difficulties, headache and loss of smell. Factors associated with persisting, impairing symptoms include increased number of symptoms at the time of testing, female sex, older age, worse self-rated physical and mental health, and feelings of loneliness preinfection.

Summary: This review highlights the importance of a control group in studies following SARS-CoV-2 infection, the need for case definitions and research to understand the outcomes of long COVID in children and young people.

Source: Stephenson T, Shafran R, Ladhani SN. Long COVID in children and adolescents. Curr Opin Infect Dis. 2022 Sep 12. doi: 10.1097/QCO.0000000000000854. Epub ahead of print. PMID: 36094094.  https://journals.lww.com/co-infectiousdiseases/Fulltext/2022/10000/Long_COVID_in_children_and_adolescents.14.aspx (Full text)

After the virus has cleared-Can preclinical models be employed for Long COVID research?

Abstract:

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) can cause the life-threatening acute respiratory disease called COVID-19 (Coronavirus Disease 2019) as well as debilitating multiorgan dysfunction that persists after the initial viral phase has resolved. Long COVID or Post-Acute Sequelae of COVID-19 (PASC) is manifested by a variety of symptoms, including fatigue, dyspnea, arthralgia, myalgia, heart palpitations, and memory issues sometimes affecting between 30% and 75% of recovering COVID-19 patients. However, little is known about the mechanisms causing Long COVID and there are no widely accepted treatments or therapeutics.

After introducing the clinical aspects of acute COVID-19 and Long COVID in humans, we summarize the work in animals (mice, Syrian hamsters, ferrets, and nonhuman primates (NHPs)) to model human COVID-19. The virology, pathology, immune responses, and multiorgan involvement are explored. Additionally, any studies investigating time points longer than 14 days post infection (pi) are highlighted for insight into possible long-term disease characteristics.

Finally, we discuss how the models can be leveraged for treatment evaluation, including pharmacological agents that are currently in human clinical trials for treating Long COVID. The establishment of a recognized Long COVID preclinical model representing the human condition would allow the identification of mechanisms causing disease as well as serve as a vehicle for evaluating potential therapeutics.

Source: Jansen EB, Orvold SN, Swan CL, Yourkowski A, Thivierge BM, Francis ME, Ge A, Rioux M, Darbellay J, Howland JG, Kelvin AA. After the virus has cleared-Can preclinical models be employed for Long COVID research? PLoS Pathog. 2022 Sep 7;18(9):e1010741. doi: 10.1371/journal.ppat.1010741. PMID: 36070309; PMCID: PMC9451097. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9451097/ (Full text)

Long Covid: where we stand and challenges ahead

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.

Source: Mantovani, A., Morrone, M.C., Patrono, C. et al. Long Covid: where we stand and challenges ahead. Cell Death Differ (2022). https://doi.org/10.1038/s41418-022-01052-6 https://www.nature.com/articles/s41418-022-01052-6 (Full text)

Differences in Long-COVID Symptoms between Vaccinated and Non-Vaccinated (BNT162b2 Vaccine) Hospitalized COVID-19 Survivors Infected with the Delta Variant

Abstract:

This study compared differences in the presence of post-COVID symptoms among vaccinated and non-vaccinated COVID-19 survivors requiring hospitalization due to the Delta (B.1.617.2) variant. This cohort study included hospitalized subjects who had survived SARS-CoV-2 infection (Delta variant) from July to August 2021 in an urban hospital in Madrid, Spain. Individuals were classified as vaccinated if they received full administration (i.e., two doses) of BNT162b2 (“Pfizer-BioNTech”) vaccines. Other vaccines were excluded. Those with just one dose of the BNT162b2 vaccine were considered as non-vaccinated.
Patients were scheduled for a telephone interview at a follow-up around six months after infection for assessing the presence of post-COVID symptoms with particular attention to those symptoms starting after acute infection and hospitalization. Anxiety/depressive levels and sleep quality were likely assessed. Hospitalization and clinical data were collected from medical records. A total comprising 109 vaccinated and 92 non-vaccinated COVID-19 survivors was included.
Vaccinated patients were older and presented a higher number of medical comorbidities, particular cardiorespiratory conditions, than non-vaccinated patients. No differences in COVID-19 onset symptoms at hospitalization and post-COVID symptoms six months after hospital discharge were found between vaccinated and non-vaccinated groups. No specific risk factor for any post-COVID symptom was identified in either group.
This study observed that COVID-19 onset-associated symptoms and post-COVID symptoms six-months after hospitalization were similar between previously hospitalized COVID-19 survivors vaccinated and those non-vaccinated. Current data can be applied to the Delta variant and those vaccinated with BNT162b2 (Pfizer-BioNTech) vaccine.
Source: Fernández-de-las-Peñas C, Ortega-Santiago R, Fuensalida-Novo S, Martín-Guerrero JD, Pellicer-Valero OJ, Torres-Macho J. Differences in Long-COVID Symptoms between Vaccinated and Non-Vaccinated (BNT162b2 Vaccine) Hospitalized COVID-19 Survivors Infected with the Delta Variant. Vaccines. 2022; 10(9):1481. https://doi.org/10.3390/vaccines10091481 https://www.mdpi.com/2076-393X/10/9/1481/htm (Full text)