The COVID-19 Pandemic and the $16 Trillion Virus

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic is the greatest threat to prosperity and well-being the US has encountered since the Great Depression. This Viewpoint aggregates mortality, morbidity, mental health conditions, and direct economic losses to estimate the total cost of the pandemic in the US on the optimistic assumption that it will be substantially contained by the fall of 2021. These costs far exceed those associated with conventional recessions and the Iraq War, and are similar to those associated with global climate change. However, increased investment in testing and contact tracing could have economic benefits that are at least 30 times greater than the estimated costs of the investment in these approaches.

Read the full text here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604733/

Also see: The Economic Cost of Long COVID: An Update: https://scholar.harvard.edu/files/cutler/files/long_covid_update_7-22.pdf

Source: Cutler DM, Summers LH. The COVID-19 Pandemic and the $16 Trillion Virus. JAMA. 2020;324(15):1495–1496. doi:10.1001/jama.2020.19759. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604733/ (Full text)

Validity of 2-Day Cardiopulmonary Exercise Testing in Male Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Introduction: Among the main characteristics of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are effort intolerance along with a prolonged recovery from exercise and post-exertional exacerbation of ME/CFS symptoms. The gold standard for measuring the severity of physical activity intolerance is cardiopulmonary exercise testing (CPET). Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients. A consecutive day CPET protocol has shown a difference on day 2 in ME/CFS patients in contrast to sedentary controls. Because of the low number of male ME/CFS patients in the published literature, and because of a possible gender difference in the clinical phenotype, the aim of this study was to examine whether the response to a 2-day CPET protocol in a larger sample of male ME/CFS patients was similar to that observed in females.

Methods: From 77 male patients, 25 male ME/CFS patients fulfilled the criteria of a 2-day CPET protocol for analysis. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were made at maximal (peak) and ventilatory threshold (VT) intensities. Data were analysed using a paired t-test.

Results: Baseline characteristics of the group were as follows. Mean age was 44 (12) years, mean BMI was 27.1 (4.4) kg/m2. Median disease duration was 10 years (IQR 7 – 13). Heart rate, systolic and diastolic blood pressure at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between <0.005 and <0.0001). All patients experienced a deterioration of performance on CPET2 as measured by the predicted and actual VO2 and workload at peak exercise and ventilatory threshold.

Conclusion: This study confirms that male ME/CFS patients have a reduction in exercise capacity in response to a consecutive day CPET. These results are similar to published results in female ME/CFS populations.

Source:

 

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)

Challenges of memory enhancers

Abstract:

40 per cent of people over the age of 65 experience some form of memory loss, called as the age related memory impairment. This might be due to hormone and proteins (Growth factors) which repair the brain cells decline with age. Certain conditions such as age, stress, disease and excessive emotional response may lead to loss of memory, loss of learning ability and altered mood and behaviour. These conditions may be treated by using nootropic agents which can help to improve learning abilities and memory.

Source: Chaudhry, Sunil. Challenges of memory enhancers. Annals of Geriatric Education and Medical Sciences; 2020/08/22. https://www.agems.in/article-details/11990 (Full text)

Pale rider: the Spanish flu of 1918 and how it changed the world

Book Review:

Pale rider: The Spanish Flu of 1918 and How it Changed the World by Laura Spinney, Public Affairs; 1st edition (September 12, 2017)

Formerly Professor of Psychiatry, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

The COVID-19 pandemic has changed life for humanity, nothing is “normal” anymore! In the last 100 years, there has not been any similar event. The common feeling among professionals, planners, press, politicians, and people is that “life will not be the same as we knew it, after the pandemic.” Understanding the likely impact of the pandemic and its consequences would be valuable to humanity in general and mental health professionals in particular. Against this current world-shaking event, it is natural to look for similar events in human history. In this, the 1918 flu is the closest event to understand a variety of aspects of the current pandemic. The book, Pale Rider: The Spanish Flu of 1918 and how it changed the world, is one of the best books in this field.[1] That many people are looking at the 1918 flu can be seen by the number of articles in the lay press that have focused on the 1918 flu.[2],[3],[4],[5],[6],[7] Even now, a new book was published as latest as July 23, 2020.[8],[9]

Nevertheless, the book, under review, has 21 chapters with attractive chapter titles such as Like a Thief in the Night; The Doctor’s Dilemma; The Wrath of God; Chalking Doors with Crosses; Good Samaritans; The Human Factor; The Green Shoots of Recovery; Alternate Histories; and Health Care for all and Melancholy Muse.

Between the first case recorded on March 4, 1918, and the last case sometime in March 1920, it killed 50–100 million people, or between 2.5% and 5% of the global population. In terms of a single event causing major loss of life, it surpassed the First World War (17 million dead) and the Second World War (60 million dead). India was specially affected and lost around 6% of its population, the greatest loss in absolute numbers of any country in the world (an estimate of 13–18 million). The book has a special focus on India,[1] presented through the lives of Mahatma Gandhi, Tagore, Munshi Premchand, and Nirala and its impact on the Independence struggle.

Mahatma Gandhi was affected by the gastric variety of flu. At Gandhi’s ashram, several prominent members of the Independence Movement were laid low with flu. Gandhi was too feverish to speak or read; he couldn’t shake a sense of doom: “All interest in living had ceased.” Interestingly, Gandhi’s reaction was: This protracted and first long illness in my life thus afforded me a unique opportunity to examine my principles and to test them. Rabindranath Tagore returned his knighthood as a reaction to the Jallianwala Bagh massacre, and observed that British were guilty of “the same kind of ignorance of the eternal laws which primitive people show when they hunt for some so-called witch to whom they ascribe the cause of their illness, while carrying the disease germs in their own blood.” Spinney observes that disease was a major preoccupation in the writing that emerged in the 1920s, where it dovetailed with ideas about the need to reform the caste system and throw off the yoke of British rule. Munshi Premchand became the self-styled “chronicler of village life” around 1918 when he was living in the United Provinces (Uttar Pradesh), where the Spanish flu claimed an estimated 2–3 million lives alone. Also living there at that time was the poet Nirala, who lost his wife and many other members of his family to the flu. He later recalled seeing the River Ganges “swollen with dead bodies.” This was the strangest time in my life. My family disappeared in the blink of an eye.

There are sections in the book describing the feelings of anxiety accompanying the acute phase of the disease, and reports of people killing themselves while delirious. Following recovery, some patients found themselves plunged into a lingering state of lassitude and despair. Norwegian epidemiologist Svenn-Erik Mamelund studied asylum records in his country from 1872 to 1929 and found that, every year, in which there was no pandemic of influenza, only a few cases were admitted of mental illness associated with flu. However, in each of the 6 years following the 1918 pandemic, the average number of such admissions was seven times higher than in those nonpandemic years (emphasis added). Mamelund speculates that the patients admitted in those 6 years were survivors of Spanish flu who were suffering from what today we would call “postviral or chronic fatigue syndrome.”

The book provides similar creative responses in a number of countries following the pandemic. The paragraph about controversies about the quarantine makes for contemporary reading: “Quarantine and other disease containment strategies place the interests of the collective over those of the individual. When the collective is very large, those strategies have to be imposed in a top-down fashion. But mandating a central authority to act in the interests of the collective potentially creates two kinds of problems. First, the collective may have competing priorities-the need to make money, or the need to raise an army-and deny or water-down the authority’s powers of enforcement. Second, the rights of individuals risk getting trampled on, especially if the authority abuses the measures placed at its disposal.”

One of the quotes from the book can portend what we can expect in the coming years in the country. Spinney notes, “The 1918 pandemic accelerated the pace of change in the first half of the twentieth century, and helped shape our modern world. It influenced the course of the First World War and arguably, contributed to the Second. It pushed India closer to Independence, South Africa closer to Apartheid, and Switzerland to the brink of Civil War. It ushered in universal healthcare and alternative medicine, our love of fresh air and our passion for sport, and it was probably responsible, at least in part, for the obsession of twentieth-century artists with all the myriad ways in which the human body can fail.”

The book made me realize that the current pandemic will bring about extensive changes. Against this expected “mental health tsunami,” there are three tasks for each one of us: firstly, to document the experiences of individuals, families, communities, and the government; secondly, to identify the social factors contributing to vulnerabilities and resilience, to guide corrective actions; and lastly, to utilize the opportunity of heightened awareness of societal-level issues, to work toward addressing the predisposing causes for higher mortality and morbidity such as inequalities, intolerances, inadequate health infrastructure, the weak welfare network to support the vulnerable, and decentralization of powers and plans to enhance community participation.

I recommend it as an essential reading during the current pandemic period.

Source: Murthy R S. Pale rider: the spanish flu of 1918 and how it changed the world. Indian J Soc Psychiatry [serial online] 2020 [cited 2022 Jul 4];36, Suppl S1:189-90. Available from: https://www.indjsp.org/text.asp?2020/36/5/189/297158

ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects

Abstract:

SARS-CoV-2 has created a global crisis. COVID-19, the disease caused by the virus, is characterized by pneumonia, respiratory distress, and hypercoagulation and can be fatal. An early sign of infection is loss of smell, taste, and chemesthesis-loss of chemical sensation. Other neurological effects of the disease have been described, but not explained. It is now apparent that many of these neurological effects (for instance joint pain and headache) can persist for at least months after infection, suggesting a sensory neuronal involvement in persistent disease.

We show that human dorsal root ganglion (DRG) neurons express the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 at the RNA and protein level. We also demonstrate that SARS-CoV-2 and coronavirus-associated factors and receptors are broadly expressed in human DRG at the lumbar and thoracic level as assessed by bulk RNA sequencing. ACE2 mRNA is expressed by a subset of nociceptors that express MRGPRD mRNA, suggesting that SARS-CoV-2 may gain access to the nervous system through entry into neurons that form free nerve endings at the outermost layers of skin and luminal organs. Therefore, DRG sensory neurons are a potential target for SARS-CoV-2 invasion of the peripheral nervous system, and viral infection of human nociceptors may cause some of the persistent neurological effects seen in COVID-19.

Source: Shiers S, Ray PR, Wangzhou A, Sankaranarayanan I, Tatsui CE, Rhines LD, Li Y, Uhelski ML, Dougherty PM, Price TJ. ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects. Pain. 2020 Nov;161(11):2494-2501. doi: 10.1097/j.pain.0000000000002051. PMID: 32826754; PMCID: PMC7572821. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572821/ (Full text)

Carnitine Palmitoyl Transferase Deficiency in a University Immunology Practice

Abstract:

Purpose: This report describes the clinical manifestations of 35 patients sent to a University Immunology clinic with a diagnosis of fatigue and exercise intolerance who were identified to have low carnitine palmitoyl transferase activity on muscle biopsies.

Recent findings: All of the patients presented with fatigue and exercise intolerance and many had been diagnosed with fibromyalgia. Their symptoms responded to treatment of the metabolic disease. Associated symptoms included bloating, diarrhea, constipation, gastrointestinal reflux symptoms, recurrent infections, arthritis, dyspnea, dry eye, visual loss, and hearing loss. Associated medical conditions included Hashimoto thyroiditis, Sjogren’s syndrome, seronegative arthritis, food hypersensitivities, asthma, sleep apnea, and vasculitis. This study identifies clinical features that should alert physicians to the possibility of an underlying metabolic disease. Treatment of the metabolic disease leads to symptomatic improvement.

Source: Bax K, Isackson PJ, Moore M, Ambrus JL Jr. Carnitine Palmitoyl Transferase Deficiency in a University Immunology Practice. Curr Rheumatol Rep. 2020 Feb 14;22(3):8. doi: 10.1007/s11926-020-0879-9. PMID: 32067119. https://pubmed.ncbi.nlm.nih.gov/32067119/

Investigating Fatigue and Exercise Intolerance in a University Immunology Clinic

Abstract:

Purpose: This manuscript reviews the experience of a University Immunology clinic with the evaluation of patients with idiopathic fatigue and exercise intolerance for the presence of metabolic disorders. Laboratory, biochemical and genetic studies were utilized in the evaluation.

Recent Findings: Of the 372 patients evaluated, 95% were found to have a treatable metabolic disorder. A defect in the glycogen storage pathway was found in 78 patients. Mitochondrial disorders were found in 258 patients. Myoadenylate deaminase deficiency was found in 7 patients. Various congenital myopathies were identified in 11 patients. Inflammatory myopathies were identified in 25 patients, 6 of whom had normal muscle enzymes on the initial evaluation.

Summary: The majority of patients (95%) referred with idiopathic fatigue and exercise intolerance after extensive evaluations were found to have underlying metabolic dysfunction. Frequently associated problems included gastrointestinal dysmotility disorders, recurrent infections, Raynaud’s, migraine headaches and various autoimmune diseases. Most patients showed symptomatic improvement with treatment of their metabolic dysfunction.

Source: Julian L A, Paul I, Molly M, John B, Lucia B. Investigating Fatigue and Exercise Intolerance in a University Immunology Clinic. Arch Rheum & Arthritis Res. 1(1): 2020. ARAR.MS.ID.000505. https://irispublishers.com/arar/fulltext/Investigating-Fatigue-and-Exercise-Intolerance-in-a-University.ID.000505.php (Full text)

Postural orthostatic tachycardia syndrome in patients of orthostatic intolerance symptoms: an ambispective study

Abstract:

Background: A Postural orthostatic tachycardia syndrome (POTS) is infrequently diagnosed in routine practice because of the variable range of symptoms that could be seen in cardiac rhythm disorders, vertigo, chronic fatigue syndrome and anxiety panic disorder. POTS is a chronic debilitating condition that affects day to day efficient working of an individual. We have planned a study to look for POTS in patients who are having orthostatic intolerance symptoms and underwent a head-up tilt table test (HUTT).

Aim: To study the prevalence of POTS in patients of orthostatic intolerance (OI) symptoms and to analyze symptomatology, its association with neurocardiogenic syncope (NCS), and its outcome.

Methods: We reviewed the medical records of 246 patients presented with symptoms of OI seen at our centre from January 2010 till March 2019. Out of them, 40 patients included, those qualifying the criteria for POTS on HUTT.

Results: The mean age of the cohort was 25.90 ± 10.33 years with a range of 15 to 55 years, and males comprised 52.5% (21/40) of total patients. The most frequent presenting orthostatic symptoms of POTS patients are loss of consciousness (77.5%), lightheadedness (75%), and palpitation (67.5%). A total of 18 patients (45%) had coexisting neurocardiogenic syncope.

Conclusion: POTS is a prevalent condition and have a significant impact on the quality of life, and the majority of patients may not present with OI symptoms during HUTT. We have to keep this possibility in young patients of transient loss of consciousness because it may coexist with NCS.

Source: Chouksey D, Rathi P, Sodani A, Jain R, Ishar HS. Postural orthostatic tachycardia syndrome in patients of orthostatic intolerance symptoms: an ambispective study. AIMS Neurosci. 2020 Dec 8;8(1):74-85. doi: 10.3934/Neuroscience.2021004. PMID: 33490373; PMCID: PMC7815479. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815479/ (Full text)

Paradigm shift to disequilibrium in the genesis of orthostatic intolerance in patients with myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Background: Orthostatic intolerance (OI) markedly impairs activities of daily living in patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome. OI is surmised to be a cardiovascular symptom correlated with cerebral hypo-perfusion and exaggerated sympathetic activation. Postural instability or disequilibrium may be part of the etiology of OI.

Methods: The study comprised 72 patients with ME (18 men, 54 women; mean age, 37 ± 10 years) who underwent neurological examinations and the 10 min standing test. We quantified disequilibrium (instability upon standing with feet together and eyes shut), ability to complete the 10 min standing test, and postural orthostatic tachycardia (POT) during the test.

Results: Disequilibrium was detected in 23/72 (32%) patients and POT in 16 (22%). Nineteen (26%) patients failed to complete the 10 min standing test; disequilibrium was significantly more common in the 19- patient subgroup than in the 53-patient test-completing subgroup (89% vs. 11%, p < 0.01). However, the rate of POT was not different between the groups (21% vs. 23%, p = 1.00). Compared with the 49 (68%) patients without disequilibrium, the 23 (32%) patients with disequilibrium were significantly more likely to have failed to complete the test (74% vs. 4%, p < 0.01). The rate of POT was comparable between the groups (23% vs. 22%, p = 1.00). Among patients with disequilibrium who failed to complete the 10 min standing test and had a previous record, 6/8 had completed the test 6-24 months earlier when all six had reported no disequilibrium.

Conclusion: Disequilibrium should be recognized as an important cause of OI in patients with ME.

Source: Miwa K, Inoue Y. Paradigm shift to disequilibrium in the genesis of orthostatic intolerance in patients with myalgic encephalomyelitis and chronic fatigue syndrome. Int J Cardiol Hypertens. 2020 May 20;5:100032. doi: 10.1016/j.ijchy.2020.100032. PMID: 33447761; PMCID: PMC7803012. https://pubmed.ncbi.nlm.nih.gov/33447761/