Taking pandemic sequelae seriously: from the Russian influenza to COVID-19 long-haulers

Honigsbaum, Mark; Krishnan, Lakshmi

doi:10.1016/s0140-6736(20)32134-6

Cited by 84 publications

(87 citation statements)

References 6 publications

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“…The influenza pandemic of 1889 and 1892 was also known as the Russian flu. Recently, Honigsbaum and Krishnan highlighted the similarities between the post-infectious neurological conditions observed at the time of the Russian flu and those of COVID-19, or long COVID [ 5 ]. The authors reported that the terminology for the long-term effects of the Russian flu included neuralgia, neurasthenia, neuritis, nerve exhaustion, grippe catalepsy, psychosis, prostration, inertia, anxiety, and paranoia, which supported that there were long-term neurological effects from this infection [ 5 ].…”

Section: The Influenza Pandemics Of 1889 and 1892 (Russian Flu)mentioning

confidence: 99%

“…The long-term neurological effects of the Spanish flu pandemic of 1918 and 1919 included Parkinsonism, catatonia, and “encephalitis lethargica” [ 5 , 6 ]. The term encephalitis lethargica was first used by the Austrian neurologist Constantin von Economo in 1917 after he identified an increased number of patients in Vienna with meningitis and delirium during the winters of 1916 and 1917 [ 7 ].…”

Section: The Spanish Flu Pandemic (1918–1919) and Encephalitis Letharmentioning

confidence: 99%

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Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID

Stefano

2021

Med Sci Monit

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Long-term sequelae of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized. However, there is still a lack of consensus regarding the terminology for this emerging chronic clinical syndrome, which includes long COVID, chronic COVID syndrome, post-COVID-19 syndrome, post-acute COVID-19, and long-hauler COVID-19. In this review, I will use the term “long COVID”. A review of the medical history and epidemiology of past pandemics and epidemics in modern literature review identifies common long-term post-infectious disorders, with the common finding of altered cognition. In the brain, the cerebral hypoxia induced by SARS-CoV-2 infection may be caused by mitochondrial dysfunction, resulting in “brain fog”. Historically, the common symptom of altered cognition has been reported during earlier pandemics, which include the influenza pandemics of 1889 and 1892 (Russian flu), the Spanish flu pandemic (1918–1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome). There are similarities between chronic fatigue syndrome and the “brain fog” described in long COVID. During past viral epidemics and pandemics, a commonality of neural targets may have increased viral survival by conformational matching. The neurological and psychiatric sequelae of SARS-CoV-2 infection, or long COVID, may have emerged from neural effects that have emerged from an invertebrate and vertebrate virosphere. This review aims to present a historical overview of infections and disorders associated with neurological and psychiatric sequelae that have shown similarities with long COVID.

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Section: The Influenza Pandemics Of 1889 and 1892 (Russian Flu)mentioning

confidence: 99%

Section: The Spanish Flu Pandemic (1918–1919) and Encephalitis Letharmentioning

confidence: 99%

Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID

Stefano

2021

Med Sci Monit

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“…Postviral syndromes following epidemics have been recognized for more than a century, and COVID-19 appears to be no exception 1 . For a subset of individuals with acute Coronavirus-19 (COVID-19) disease, symptoms may persist beyond a month 2 , with some patients reporting symptoms at least 6 months later.…”

Section: Introductionmentioning

confidence: 99%

Persistence of symptoms up to 10 months following acute COVID-19 illness

Perlis

Green

Santillana

et al. 2021

Preprint

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Importance: COVID-19 symptoms are increasingly recognized to persist among a subset of individual following acute infection, but features associated with this persistence are not well-understood. Objective: We aimed to identify individual features that predicted persistence of symptoms over at least 2 months at the time of survey completion. Design: Non-probability internet survey. Participants were asked to identify features of acute illness as well as persistence of symptoms at time of study completion. We used logistic regression models to examine association between sociodemographic and clinical features and persistence of symptoms at or beyond 2 months. Setting: Ten waves of a fifty-state survey between June 13, 2020 and January 13, 2021. Participants: 6,211 individuals who reported symptomatic COVID-19 illness confirmed by positive test or clinician diagnosis. Exposure: symptomatic COVID-19 illness Results: Among 6,211 survey respondents reporting COVID-19 illness, with a mean age of 37.8 (SD 12.2) years and 45.1% female, 73.9% white, 10.0% Black, 9.9% Hispanic, and 3.1% Asian, a total of 4946 (79.6%) had recovered within less than 2 months, while 491 (7.9%) experienced symptoms for 2 months or more. Of the full cohort, 3.4% were symptomatic for 4 months or more and 2.2% for 6 months or more. In univariate analyses, individuals with persistent symptoms on average reported greater initial severity. In logistic regression models, older age was associated with greater risk of persistence (OR 1.10, 95% CI 1.01-1.19 for each decade beyond 40); otherwise, no significant associations with persistence were identified for gender, race/ethnicity, or income. Presence of headache was significantly associated with greater likelihood of persistence (OR 1.44, 95% CI 1.11-1.86), while fever was associated with diminished likelihood of persistence (OR 0.66, 95% CI 0.53-0.83). Conclusion and Relevance: A subset of individuals experience persistent symptoms from 2 to more than 10 months after acute COVID-19 illness, particularly those who recall headache and absence of fever. In light of this prevalence, strategies for predicting and managing such sequelae are needed. Trial Registration: NA

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“…8.9 An increasing new patient population called the "long haulers" consists of individuals who were not serious enough to be hospitalized but suffer lingering symptoms after several months, and is estimated by the CDC to be 20-30% of confirmed COVID19-positive persons. [10][11][12] Several studies have also revealed a strong association of the male sex being a risk factor for increased disease severity and mortality (nearly twice the rate). 13,14 It is thought that the severity of COVID-19 is brought about by aberrant immune responses to the SARS-CoV-2 infection which are highly variable among patient populations, but are often characterized by an aggressive response by inflammatory processes reminiscent of a cytokine release syndrome or "CRS", mobilization of an abnormal cellular milieu, and the triggering of autoimmune pathways.…”

Section: Introductionmentioning

confidence: 99%

Neural epidermal growth factor-like 1 protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 transgenic mice infected with SARS-CoV-2

Biswas

Eaker

Soni

et al. 2021

Preprint

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Coronavirus disease 2019 (COVID-19) is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is a worsening global pandemic. COVID-19 has caused at least 1.7 million deaths worldwide and over 300,000 in the United States. Recently, two promising vaccines are being administered in several countries. However, there remains an urgent need for a therapeutic treatment for COVID-19 patients with severe respiratory damage that can lead to intensive care, prolonged hospitalization, or mortality. Moreover, an increasing population of patients manifest lingering disabling symptoms (called Long Haulers). Here, we tested the efficacy of a recombinant neural epidermal growth factor like 1 protein variant (NELL1-NV1) in a COVID-19 mouse model, transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor (tg-mice hACE2) infected with SARS-CoV-2. The administration of NELL1-NV1 to SARS-CoV-2-infected tg-mice hACE2 significantly improved clinical health score and increased survival. Analyses of bronchoalveolar (BAL) fluid demonstrated decreased levels of several cytokines and chemokines (IFN-γ, IL-10, IL-12 p70, CXCL-10/IP-10, MIG and Rantes), in NV1-treated treated mice compared to controls. Cytokines including IL-1α, IL-9, IL-6, LIX/CXCL5, KC/CXCL1, MIP-2/CXCL2, MIP-1α/CCL3, and G-CSF, critical to immune responses such as neutrophil recruitment, viral clearance and vascularization, were increased compared to controls. Our data suggest the potential of NELL1-NV1-based therapy to mitigate the cytokine storm, modulate the abnormal immune response and repair respiratory tissue damage in COVID-19 patients.

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Taking pandemic sequelae seriously: from the Russian influenza to COVID-19 long-haulers

Cited by 84 publications

References 6 publications

Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID

Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID

Persistence of symptoms up to 10 months following acute COVID-19 illness

Neural epidermal growth factor-like 1 protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 transgenic mice infected with SARS-CoV-2

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