Post COVID syndrome: A novel challenge and threat to international health

Abstract:

The global pandemic caused by the SARS-CoV-2 virus has affected every continent worldwide. The novelty of this virus, its mutations and the rapid speed and unprecedented rate at which it has torn through the global community has in turn lead to an innate lack of knowledge and information about the actual disease caused and the severity of the complications associated with COVID-19.

The SARS-CoV-2 virus has been infecting individuals since 2019 and now as of 2022 has been circulating for just over 2 years within the global populous. As the number of cases have risen globally over this period (some of which having contracted the virus twice) further endeavours have been undertaken to better understand the pathogenesis and natural progression of the disease. A condition reported in some cases with extended bouts of sickness or symptoms following the initial infection with COVID was labelled “long COVID” towards the earlier phases of the pandemic (in the spring of 2020), but has only recently gained the global media and medical attention due to its affliction of more individuals on a global basis and has thus warranted further investigation.

Long COVID is described as a persistent, long-term state of poor health following an infection with COVID-19. The effect of Long COVID is multisystemic in nature with a wide array of signs and symptoms. The most commonly reported clinical features of long COVID are: headaches, myalgia, chest pain, rashes, abdominal pain, shortness of breath, palpitations, anosmia, persistent cough, brain fogs, forgetfulness, depression, insomnia, fatigue and anxiety. This research aims to explore the symptomatology, pathophysiology as well as the treatment and prevention of Long COVID.

Source: Banerjee I, Robinson J, Leclézio A, Sathian B, Banerjee I. Post COVID syndrome: A novel challenge and threat to international health. Nepal J Epidemiol. 2022 Jun 30;12(2):1215-1219. doi: 10.3126/nje.v12i2.46149. PMID: 35974973; PMCID: PMC9374107.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374107/ (Full text)

A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity

Abstract:

A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively.

Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy.

Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.

Source: Kedor C, Freitag H, Meyer-Arndt L, Wittke K, Hanitsch LG, Zoller T, Steinbeis F, Haffke M, Rudolf G, Heidecker B, Bobbert T, Spranger J, Volk HD, Skurk C, Konietschke F, Paul F, Behrends U, Bellmann-Strobl J, Scheibenbogen C. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat Commun. 2022 Aug 30;13(1):5104. doi: 10.1038/s41467-022-32507-6. PMID: 36042189. https://www.nature.com/articles/s41467-022-32507-6 (Full text)

Long-COVID Clinical Features and Risk Factors: A Retrospective Analysis of Patients from the STOP-COVID Registry of the PoLoCOV Study

Abstract:

Despite recovering from the acute phase of coronavirus disease (COVID-19), many patients report continuing symptoms that most commonly include fatigue, cough, neurologic problems, hair loss, headache, and musculoskeletal pain, a condition termed long-COVID syndrome. Neither its etiopathogenesis, nor its clinical presentation or risk factors are fully understood. Therefore, the purpose of this study was to retrospectively evaluate the most common symptoms of long-COVID among patients from the STOP COVID registry of the PoLoCOV study, and to search for risk factors for development of the syndrome.

The registry includes patients who presented to the medical center for persistent clinical symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The analysis included data from initial presentation and at three-month follow-up. Of the 2218 patients, 1569 (70.7%) reported having at least one symptom classified as long-COVID syndrome three months after recovery from the initial SARS-CoV-2 infection. The most common symptoms included chronic fatigue (35.6%\), cough (23.0%), and a set of neurological symptoms referred to as brain fog (12.1%).

Risk factors for developing long-COVID syndrome included female gender (odds ratio [OR]: 1.48, 95% confidence intervals [CI] [1.19-1.84]), severe COVID-19 (OR: 1.56, CI: 1.00-2.42), dyspnea (OR: 1.31, CI: 1.02-1.69), and chest pain (OR: 1.48, CI: 1.14-1.92). Long-COVID syndrome represents a significant clinical and social problem. The most common clinical manifestations are chronic fatigue, cough, and brain fog. Given the still-limited knowledge of long-COVID syndrome, further research and observation are needed to better understand the mechanisms and risk factors of the disease.

Source: Chudzik M, Babicki M, Kapusta J, Kałuzińska-Kołat Ż, Kołat D, Jankowski P, Mastalerz-Migas A. Long-COVID Clinical Features and Risk Factors: A Retrospective Analysis of Patients from the STOP-COVID Registry of the PoLoCOV Study. Viruses. 2022 Aug 11;14(8):1755. doi: 10.3390/v14081755. PMID: 36016376; PMCID: PMC9415629. https://www.mdpi.com/1999-4915/14/8/1755/htm (Full text)

COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis

Abstract:

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect. Mechanisms underlying these brain symptoms remain understudied.

Here we report that SARS-CoV-2-infected hamsters exhibit a lack of viral neuroinvasion despite aberrant blood-brain barrier permeability. Hamsters and patients deceased from coronavirus disease 2019 (COVID-19) also exhibit microglial activation and expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the medulla oblongata, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uraemia or trauma. In the hippocampal dentate gyrus of both COVID-19 hamsters and humans, we observed fewer neuroblasts and immature neurons.

Protracted inflammation, blood-brain barrier disruption and microglia activation may result in altered neurotransmission, neurogenesis and neuronal damage, explaining neuropsychiatric presentations of COVID-19. The involvement of the hippocampus may explain learning, memory and executive dysfunctions in COVID-19 patients.

Source: Soung AL, Vanderheiden A, Nordvig AS, Sissoko CA, Canoll P, Mariani MB, Jiang X, Bricker T, Rosoklija GB, Arango V, Underwood M, Mann JJ, Dwork AJ, Goldman JE, Boon ACM, Boldrini M, Klein RS. COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis. Brain. 2022 Aug 25:awac270. doi: 10.1093/brain/awac270. Epub ahead of print. PMID: 36004663. https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awac270/6672950?login=false  (Full text)

Correlation of respiratory muscle function and cardiopulmonary exercise testing in post-acute COVID-19 syndrome

To the editors,

We read the paper published by Hennigs et al. [] with great interest and thank the authors for shifting the focus to studying respiratory muscle function in Post-COVID-19 patients. The authors report striking pathological findings of mouth occlusion pressure (MOP) measurements in previously hospitalized but also non-hospitalized patients presenting with post-acute COVID-19 syndrome (PACS). In their study, Hennigs and co-authors found a high proportion of patients, more frequently females, with decreased maximum inspiratory pressure (MIP, or PImax), suggesting impairment of respiratory muscle strength. Additionally, their data indicate that increased neuroventilatory or central ventilatory drive (P0.1) may have a role in perceived respiratory distress in patients suffering from Post-COVID-19 fatigue. With this letter, we would like to share complementary data from a case series correlating MIP and P0.1 with cardiopulmonary exercise testing (CPET) in patients with PACS. Furthermore, we aim to elaborate on the limitations of MOP measurements, particularly MIP.

Read the rest of this article HERE.

Source: Leo F, Bülau JE, Semper H, Grohé C. Correlation of respiratory muscle function and cardiopulmonary exercise testing in post-acute COVID-19 syndrome. Infection. 2022 Aug 16:1–4. doi: 10.1007/s15010-022-01899-4. Epub ahead of print. PMID: 35972679; PMCID: PMC9379900. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379900/ (Full text)

Long-COVID neurological symptoms are associated with D-dimer levels in COVID-19 patients

Abstract:

Background: Coronavirus disease 2019 (COVID-19) is a disease designated as a global pandemic by the WHO that can manifest clinically as neurological disorders that can occur in the acute phase or after the acute phase (long COVID-19), such as headache, myalgia, anosmia, and cognitive impairment. These neurological disorders as symptoms of long COVID-19 are presumably caused by hypercoagulable conditions characterized by an increase in D-dimer level. This study aims to determine the correlation of long COVID-19 neurological symptoms with hypercoagulable conditions and the role of D-dimer as a biomarker of long COVID-19 neurological symptoms.

Methods: This was a cross-sectional study involving 31 patients with long COVID-19 symptoms. Admitted long COVID-19 cases with recorded D-dimer levels and definitive outcomes were included consecutively. Long COVID-19 neurological symptoms were collected. D-dimer level was measured using immunofluorescence assay and reported in fibrinogen equivalent units (ìg/mL). The correlation between D-dimer levels and neurological clinical manifestations was assessed by using ordinal regression analysis. The p-value of <0.05 was considered statistically significant.

Results: The mean age of the subjects was 38.81 ± 11.58 years and 18 (58.06%) were female. Long COVID neurological symptoms comprised myalgia, anosmia and cephalgia, and most subjects complained of myalgia (80.65%). On multivariable analysis, long-COVID-19 neurological symptoms were significantly correlated with D-dimer [odds ratio (OR) = 1.05; p=0.020].

Conclusion: The number of neurological long COVID symptoms were significantly correlated with level of D-Dimer. Ultimately, more clarity is needed on the neurological impact of COVID-19, its diagnosis, and its treatment.

Source: Mirawati, D. K., Budianto, P., Danuaji, R., Subandi, S., Ristinawati, I., & Prabaningtyas, H. R. (2022). Long-COVID neurological symptoms are associated with D-dimer levels in COVID-19 patients. Universa Medicina41(2), 169–175. https://doi.org/10.18051/UnivMed.2022.v41.169-175 https://univmed.org/ejurnal/index.php/medicina/article/view/1246

Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients

Abstract:

Background and objectives: Latest studies have revealed that an increasing number of Corona Virus Disease of 2019 (COVID-19) patients may continue to feel symptoms after the acute phase. This study aimed to evaluate the prevalence of musculoskeletal symptoms after the acute phase of COVID-19 and its associated factors.

Methods: We designed a cross-sectional study from January 2021 to April 2021. An online questionnaire was designed and sent to patients who had recovered from COVID-19. The questionnaire contained questions on participants’ demographic characteristics, COVID-19 course at its acute phase, and musculoskeletal symptoms after recovering from COVID-19. Musculoskeletal symptoms associations with patients’ characteristic and COVID-19 course was evaluated.

Result: 239 patients, including 72 (30.1%) males and 167 (69.9%) females with a mean age of 37.96 years (SD=11.19), were included in the study. 98.74% of our patients had experienced at least one musculoskeletal symptom after recovering from COVID-19, and the most common symptom was fatigue, as 91.2% of participants experienced this symptom, followed by myalgia, headache, and low back pain. High BMI, hospitalization, and ICU admission were associated with a higher risk of musculoskeletal symptoms.

Conclusion: This study indicated a high prevalence of persistent musculoskeletal symptoms among patients who recovered from COVID-19. Modifiable factors, such as BMI, can be targeted to reduce the prevalence of musculoskeletal symptoms in COVID-19 survivors and reduce its burden.

Source: Azadvari M, Haghparast A, Nakhostin-Ansari A, Emami Razavi SZ, Hosseini M. Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients. Heliyon. 2022 Aug 11:e10148. doi: 10.1016/j.heliyon.2022.e10148. Epub ahead of print. PMID: 35971463; PMCID: PMC9367176. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367176/ (Full text)

Post-COVID-19 neurologic syndrome: Another legacy of the pandemic

Abstract:

COVID-19 quickly escalated to a global pandemic in 2020. As research on the topic continues, the medical community has found that this acute illness can cause a new chronic illness: postacute sequelae of SARS-CoV-2 (PASC). Some patients with PASC develop predominately neurologic sequelae (post-COVID-19 neurologic syndrome or PCNS). This article describes PASC and PCNS, their proposed pathogenicity and possible neurovirulence mechanisms, symptoms, and treatment recommendations.

Source: Luciew, Joshua D. MPAS, PA-C; Erickson, Rodney A. MD; Kaufman, Tara K. MD. Post-COVID-19 neurologic syndrome: Another legacy of the pandemic. JAAPA: August 9, 2022 – Volume – Issue – 10.1097/01.JAA.0000854524.40560.f3 doi: 10.1097/01.JAA.0000854524.40560.f3  https://journals.lww.com/jaapa/Fulltext/9900/Post_COVID_19_neurologic_syndrome__Another_legacy.18.aspx (Full text)

Comorbidity of long COVID and psychiatric disorders after a hospitalisation for COVID-19: a cross-sectional study

Abstract:

Objectives: Long COVID is a major public health issue. Whether long COVID is comorbid with psychiatric disorders remains unclear. Here, we investigate the association between long COVID, psychiatric symptoms and psychiatric disorders.

Design: Cross-sectional.

Settings: Bicêtre Hospital, France, secondary care.

Participants: One hundred seventy-seven patients admitted in intensive care unit during acute phase and/or reporting long COVID complaints were assessed 4 months after hospitalisation for an acute COVID.

Main outcome measures: Eight long COVID complaints were investigated: fatigue, respiratory and cognitive complaints, muscle weakness, pain, headache, paraesthesia and anosmia. The number of complaints, the presence/absence of each COVID-19 complaint as well as lung CT scan abnormalities and objective cognitive impairment) were considered. Self-reported psychiatric symptoms were assessed with questionnaires. Experienced psychiatrists assessed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based diagnoses of psychiatric disorders.

Results: One hundred and fifteen (65%) patients had at least one long COVID complaint. The number of long COVID complaints was associated with psychiatric symptoms. The number of long COVID complaints was higher in patients with psychiatric disorders (mean (m) (SD)=2.47 (1.30), p<0.05), new-onset psychiatric disorders (m (SD)=2.41 (1.32), p<0.05) and significant suicide risk (m (SD)=2.67 (1.32), p<0.05) than in patients without any psychiatric disorder (m (SD)=1.43 (1.48)). Respiratory complaints were associated with a higher risk of psychiatric disorder and new-onset psychiatric disorder, and cognitive complaints were associated with a higher risk of psychiatric disorder.

Conclusions: Long COVID is associated with psychiatric disorders, new-onset psychiatric disorders and suicide risk. Psychiatric disorders and suicide risk should be systematically assessed in patients with long COVID.

Source: Gasnier M, Choucha W, Radiguer F, Faulet T, Chappell K, Bougarel A, Kondarjian C, Thorey P, Baldacci A, Ballerini M, Ait Tayeb AEK, Herrero H, Hardy-Leger I, Meyrignac O, Morin L, Lecoq AL, Pham T, Noel N, Jollant F, Montani D, Monnet X, Becquemont L, Corruble E, Colle R; COMEBAC study group. Comorbidity of long COVID and psychiatric disorders after a hospitalisation for COVID-19: a cross-sectional study. J Neurol Neurosurg Psychiatry. 2022 Aug 11:jnnp-2021-328516. doi: 10.1136/jnnp-2021-328516. Epub ahead of print. PMID: 35953265.  https://jnnp.bmj.com/content/early/2022/08/10/jnnp-2021-328516 (Full text)

Symptom burden and immune dynamics 6 to 18 months following mild SARS-CoV-2 infection -a case-control study

Abstract:

Background: The burden and duration of persistent symptoms after non-severe COVID-19 remains uncertain. This study aimed to assess post-infection symptom trajectories in home-isolated COVID-19 cases compared to age- and time-period matched seronegative controls, and investigate immunological correlates of long COVID.

Methods: A prospective case-control study conducted between February 28th and April 4th 2020 included home-isolated COVID-19 cases followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched SARS-CoV-2 naive controls. We collected clinical data at baseline, 6, 12 and 18 months post-infection, and blood samples at 2, 4, 6 and 12 months for analysis of SARS-CoV-2 specific humoral and cellular responses.

Results: Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared to controls, adult cases had a high risk of fatigue (27% excess risk, gender and comorbidity adjusted odds ratio [aOR] 5.86, 95% confidence interval [CI]3.27-10.5), memory problems (21% excess risk, aOR 7.42, CI 3.51-15.67), concentration problems (20% excess risk, aOR 8.88, CI 3.88-20.35), and dyspnea (10% excess risk, aOR 2.66, CI 1.22-5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%, CI 1.5, 21.5, p = 0.024) and among women (excess risk 18.7%, CI 4.4, 32.9, p = 0.010). Longitudinal spike IgG was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4 + TCRβ depth was significantly associated with both dyspnea and number of symptoms at 12 months.

Conclusions: This study documents a high burden of persisting symptoms after mild COVID-19, and suggest that infection induced SARS-CoV-2 specific immune responses may influence long-term symptoms.

Source: Fjelltveit EB, Blomberg B, Kuwelker K, Zhou F, Onyango TB, Brokstad KA, Elyanow R, Kaplan IM, Tøndel C, Mohn KGI, Özgümüş T, Cox RJ, Langeland N; Bergen COVID-19 Research Group. Symptom burden and immune dynamics 6 to 18 months following mild SARS-CoV-2 infection -a case-control study. Clin Infect Dis. 2022 Aug 12:ciac655. doi: 10.1093/cid/ciac655. Epub ahead of print. PMID: 35959897; PMCID: PMC9384725. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384725/ (Full text)