Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol

Abstract:

Background: Emerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy.

Methods: A prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey.

Results: Of 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47-169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p < 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1-3 months and p 0.01 at 6-9 months follow up), but not in children. We found no significant correlation between adults and children symptoms. In the paediatric group, there was a significant difference in persisting symptoms between those with confirmed SARS-CoV-2 infection compared to controls at 1-3 months follow up, but not at 6-9 months. Conversely, positive adults had a higher frequency of persisting symptoms at both follow-up assessments.

Conclusion: Our data highlights that children can experience persistent multisystemic symptoms months after diagnosis of mild acute SARS-CoV-2 infection, although less frequently and less severely than co-habitant adults. There was no correlation between symptoms experienced by adults and children living in the same household. Our data highlights an urgent need for studies to characterise PASC in whole populations and the wider impact on families.

Source: Buonsenso D, Munblit D, Pazukhina E, Ricchiuto A, Sinatti D, Zona M, De Matteis A, D’Ilario F, Gentili C, Lanni R, Rongai T, Del Balzo P, Fonte MT, Valente M, Zampino G, De Rose C, Sigfrid L, Valentini P; FIMP-Roma. Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol. Front Pediatr. 2022 Apr 21;10:834875. doi: 10.3389/fped.2022.834875. PMID: 35529336; PMCID: PMC9070551.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070551/ (Full text)

Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study

Abstract:

Background: The long-COVID syndrome (LCS), defined by residual symptoms from acute COVID-19 for <60 days, affects about one-third of all COVID survivors and is an emerging public health challenge. Empirical data about the range of symptoms or the utility of acupuncture alone for the LCS are very limited.

Case: This observational case study of a 46-year-old male with LCS was conducted to preliminarily define the range of symptoms, a Traditional Chinese Medicine (TCM) diagnostic structure, and evaluate the potential utility of prescribed acupuncture for LCS.

Results: The primary TCM diagnostic patterns from this patient’s LCS presentation included Lung Qi and Yin Deficiency, Qi and Blood Stagnation, and Spleen Qi Deficiency with dampness. Acupuncture for this patient was associated with reduced symptoms and signs of LCS.

Conclusion: A preliminary TCM diagnostic structure for LCS was defined. Acupuncture appears to have been helpful for a patient with LCS. Further research is needed to demonstrate the efficacy of acupuncture and/or other TCM modalities for LCS.

Source: Michael Hollifield, Karen Cocozza, Teresa Calloway, Jennifer Lai, Brianna Caicedo, Kala Carrick, Ruth Alpert, and An-Fu Hsiao. Medical Acupuncture (ahead of print). http://doi.org/10.1089/acu.2021.0088 https://www.liebertpub.com/doi/full/10.1089/acu.2021.0088  (Full text)

Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome

Abstract:

Background: Long COVID (coronavirus disease 2019) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. In this report, we propose a model for the pathophysiology of the long COVID presentation based on increased proinflammatory cytokine production that results from the persistence of the SARS-CoV-2 virus or one of its molecular components. Associated with this hyperproduction of inflammatory cytokines is a heightened activity of nuclear factor κ B (NF-κB) and p38 mitogen-activated protein kinase signaling pathways that regulate cytokine production.

Objective: The purpose of the present report was to review the causes of long COVID syndrome and suggest ways that can provide a basis for a better understanding of the clinical symptomatology for the of improved diagnostic and therapeutic procedures for the condition.

Methods: Extensive research was conducted in medical literature data bases by applying terms such as “long COVID” associated with “persistence of the SARS-CoV-2 virus” “spike protein’ “COVID-19” and “biologic therapies.”

Results and Conclusions: In this model of the long COVID syndrome, the persistence of SARS-CoV-2 is hypothesized to trigger a dysregulated immune system with subsequent heightened release of proinflammatory cytokines that lead to chronic low-grade inflammation and multiorgan symptomatology. The condition seems to have a genetic basis, which predisposes individuals to have a diminished immunologic capacity to completely clear the virus, with residual parts of the virus persisting. This persistence of virus and resultant hyperproduction of proinflammatory cytokines are proposed to form the basis of the syndrome.

Source: Buonsenso D, Piazza M, Boner AL, Bellanti JA. Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome. Allergy Asthma Proc. 2022 May 1;43(3):187-193. doi: 10.2500/aap.2022.43.220018. PMID: 35524358. https://pubmed.ncbi.nlm.nih.gov/35524358/ https://www.ingentaconnect.com/content/ocean/aap/2022/00000043/00000003/art00003;jsessionid=pp9ea7gev7kv.x-ic-live-01#  (Full text available as download)

Long COVID: aiming for a consensus

The spectrum of signs and symptoms that can newly occur and persist for months to years after SARS-CoV-2 infection was initially named long COVID. This term was collectively created by the patient community in the spring of 2020, and was later followed by other terms, such as post-COVID-19 condition, post-acute sequelae of SARS-CoV-2 infection, and post-COVID syndrome. This condition can affect different organs and body systems, with a wide range of signs and symptoms reported. Given the magnitude of the sequelae of SARS-CoV-2 infection, it is essential to agree upon the nomenclature and definition to assess its incidence, subtypes, and severity. This process cannot be left to agencies, health-care providers, or researchers alone, but requires extensive consultation, notably including the people affected.

In early 2021, WHO established technical working groups to provide a clinical case definition for this condition and amplified the calls of patient groups for recognition, research, and rehabilitation. A rapidly increasing number of studies started to investigate the incidence and prevalence, features, and risk factors of the prolonged sequelae of SARS-CoV-2 infection, the underlying mechanisms, and case management approaches.

There are concerns about differences in terminology, with some public health experts and policy makers avoiding the term long COVID. The use of different terms can raise worries, especially among those with lived experience of the condition who originally coined the term long COVID. Many issues have been raised by patient-researchers and other adopters of the term. One issue is epistemic injustice in medicine, including the poor recognition of patient-led expertise. Patient perspectives emphasise the tradition in medical history that those who first identify and describe a condition, name it. In the case of long COVID, it was people with lived experience of it who brought it to the world’s attention and described it via a wide range of methods. The first publication on prolonged symptoms of COVID-19 was authored by patient-researchers with long COVID, later known as the Patient-Led Research Collaborative. Another issue is that the severity, features, and urgency of long COVID—as highlighted by patients—are not fully addressed within the framework of other terms and definitions. Long COVID remains the patient-preferred term.

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Source: Munblit D, O’Hara ME, Akrami A, Perego E, Olliaro P, Needham DM. Long COVID: aiming for a consensus [published online ahead of print, 2022 May 4]. Lancet Respir Med. 2022;S2213-2600(22)00135-7. doi:10.1016/S2213-2600(22)00135-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067938/ (Full text)

Caring for the carers: understanding long covid in our diverse healthcare workforce

In the United Kingdom (UK), there have been over 21.4 million confirmed cases of covid-19 as of April 2022.1 Evidence has emerged that some patients are experiencing long term symptoms and complications that extend beyond the acute infection phase, which is now widely known as long covid.23 According to the most recent UK Government’s Office for National Statistics data (April 2021), approximately 1.7 million individuals in the UK reported experiencing covid-19 symptoms for longer than four weeks.4 Of these, 690% had covid-19 for the first time at least 12 weeks previously, and 45% had covid-19 at least a year ago.4

As the covid-19 pandemic has progressed, there has been increasing evidence that healthcare workers, especially those from ethnic minority backgrounds, may be at particularly high risk of poor physical and mental health outcomes.5 This is likely to be attributed to the many challenges that healthcare workers face while working in these circumstances, including the high work demand, shortage of staff, lack of personal protective equipment (PPE), rapid changes in protocols and guidance, and long working hours, as well as their increased risk of covid-19 infection and severe disease.56 As a result, healthcare workers may also be more likely than the general population to be affected by long covid, with a disproportionate burden among ethnic minorities.

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Source: Amani Al-Oraibi, Katherine Woolf, Laura B Nellums, Carolyn Tarrant, Habib Naqvi, Manish Pareek. Caring for the carers: understanding long covid in our diverse healthcare workforce. BMJ 2022;377:o1152 https://www.bmj.com/content/377/bmj.o1152.full (Full text)

Aromatherapy blend of thyme, orange, clove bud, and frankincense boosts energy levels in post-COVID-19 female patients: A randomized, double-blinded, placebo controlled clinical trial

Abstract:

Background: A large proportion of individuals who have recovered from an acute COVID-19 infection continue to experience symptoms months later. Post-acute COVID-19 (long-haul COVID-19) can range from serious complications to quality of life symptoms such as fatigue or insomnia. The purpose of this study was to evaluate the potential for inhalation of essential oils to improve energy levels among otherwise healthy female survivors of acute COVID-19 who experience a lack of energy more than five months after recovery. This study was conducted in the United States in late 2021.

Method: This was a randomized double blind, placebo controlled trial to evaluate the potential for inhalation of Longevity™, a proprietary essential oil blend manufactured by Young Living Essential Oils (Lehi, Utah, USA), on energy levels among female survivors of COVID-19 who continue to experience fatigue more than 5 months recovery from the acute infection. Forty women were randomized to two groups: intervention and placebo. Both groups inhaled the assigned product twice daily for fourteen consecutive days. Fatigue scores were measured using the Multidimensional Fatigue Symptom Inventory (MFSI). Secondary outcomes included scores on each of the MFSI’s ten subscales.

Results: Individuals who inhaled the essential oil blend for 2 weeks had significantly lower fatigue scores after controlling for baseline scores, employment status, BMI, olfactory function, and time since diagnosis, with a large effect size (F (1,39) = 6.15, p = .020, partial eta squared = 0.198). Subscale analysis identified subscales of vigor, as well as global, behavioral, general, and mental fatigue as benefiting from the intervention. This study provides evidence that a proprietary aromatherapy blend can significantly improve energy levels among women who are experiencing fatigue after recovering from COVID-19.

Source: Hawkins J, Hires C, Keenan L, Dunne E. Aromatherapy blend of thyme, orange, clove bud, and frankincense boosts energy levels in post-COVID-19 female patients: A randomized, double-blinded, placebo controlled clinical trial. Complement Ther Med. 2022 Aug;67:102823. doi: 10.1016/j.ctim.2022.102823. Epub 2022 Mar 25. PMID: 35341944; PMCID: PMC8949693. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949693/ (Full text)

Case Report: Therapeutic and immunomodulatory effects of plasmapheresis in long-haul COVID

Abstract:

Many patients with COVID-19 experience a range of debilitating symptoms months after being infected, a syndrome termed long-haul COVID. A 68-year-old male presented with lung opacity, fatigue, physical and cognitive weaknesses, loss of smell and lymphocytopenia. After rounds of therapeutic plasma exchange (TPE), the patient returned to normal activities and work. Mechanistically in the patient’s peripheral blood mononuclear cells (PBMCs), markers of inflammatory macrophages diminished and markers of lymphocytes, including natural killer (NK) cells and cytotoxic CD8 T-cells, increased. Circulating inflammatory proteins diminished, while positive regulators of tissue repair increased. This case study suggests that TPE has the capacity to treat long-haul COVID.

Source: Kiprov DD, Herskowitz A, Kim D, Lieb M, Liu C, Watanabe E, Hoffman JC, Rohe R, Conboy MJ, Conboy IM. Case Report: Therapeutic and immunomodulatory effects of plasmapheresis in long-haul COVID. F1000Res. 2021 Nov 24;10:1189. doi: 10.12688/f1000research.74534.2. PMID: 35464182; PMCID: PMC9021669. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021669/ (Full text)

Prevalence of vitamin D deficiency among patients attending Post COVID-19 follow-up clinic: a cross-sectional study

Abstract:

Objective: Post-COVID-19 syndrome appears to be a multi-organ illness with a broad spectrum of manifestations, occurring after even mild acute illness. Limited data currently available has suggested that vitamin D deficiency may play a role in COVID-19 cases. However, to our knowledge, no study has examined the frequency of vitamin D deficiency in post-COVID-19 cases and its effect on the symptom severity. The aim of this study is to both screen the frequency of vitamin D deficiency in post-COVID-19 syndrome patients and to study its relation to persistent symptoms.

Patients and methods: A cross-sectional, single-center study was conducted involving all cases attending post-COVID-19 follow-up clinic from November 2020 to May 2021. Complete history, clinical examination, and laboratory analysis [kidney functions, serum calcium, C-reactive protein, serum ferritin, Serum 25-(OH) vitamin D] was done as well as HRCT chest.

Results: The study included 219 post-COVID-19 cases, 84% had deficient vitamin D levels (< 20 ng/dL); 11.4% had insufficient level (20-30 ng/dL) and only 4.9 % reported normal level. There was no link between levels of vitamin D with either the acute or post-COVID-19 symptoms in the studied groups.

Conclusions: Despite the prevalence of vitamin D deficiency among the study population, no association was observed between the levels of vitamin D and post-COVID-19 symptoms. It appears that post-COVID-19 syndrome pathophysiology involves a more complex interaction with the immune system. Dedicated clinical trials are advised to better study vitamin D levels and the related disease severity in COVID-19 patients.

Source: Mohamed Hussein AAR, Galal I, Amin MT, Moshnib AA, Makhlouf NA, Makhlouf HA, Abd-Elaal HK, Kholief KMS, Abdel Tawab DA, Kamal Eldin KA, Attia AM, Othman AEA, Shah J, Aiash H. Prevalence of vitamin D deficiency among patients attending Post COVID-19 follow-up clinic: a cross-sectional study. Eur Rev Med Pharmacol Sci. 2022 Apr;26(8):3038-3045. doi: 10.26355/eurrev_202204_28635. PMID: 35503606. https://www.europeanreview.org/article/28635 (Full text)

Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician

Abstract:

Purpose of review: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection.

Recent findings: Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications.

Source: Tobler DL, Pruzansky AJ, Naderi S, Ambrosy AP, Slade JJ. Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician. Curr Atheroscler Rep. 2022 May 4:1–8. doi: 10.1007/s11883-022-01032-8. Epub ahead of print. PMID: 35507278; PMCID: PMC9065238. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065238/ (Full text)

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series

Abstract:

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified.

(Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).

Source: Baldi BG, Fabro AT, Franco AC, Machado MHC, Prudente RA, Franco ET, Marrone SR, Vale SAD, Cezare TJ, Moraes MPT, Ferreira EVM, Albuquerque ALP, Sawamura MVY, Tanni SE. Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series. J Bras Pneumol. 2022 Apr 29;48(3):e20210438. doi: 10.36416/1806-3756/e20210438. PMID: 35508067; PMCID: PMC9064656. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9064656/  (Full text)