The Psychiatric Consequences of Long-COVID: A Scoping Review

The COVID-19 pandemic has represented a new form of traumatic event, affecting the general population worldwide and causing severe disruption of daily routine. A new urgent concern is related to the burden associated with COVID-19 symptoms that persist beyond the onset of infection, the so-called long-COVID syndrome.
The present paper aims to: (1) describe the most frequent psychiatric symptoms reported by patients affected by long-COVID syndrome; (2) evaluate methodological discrepancies among the available studies; (3) inform clinicians and policy-makers on the possible strategies to be promoted in order to manage the psychiatric consequences of long-COVID syndrome.
Twenty-one papers have been included in the present review, mostly with a cross-sectional or cohort design. Significant heterogeneity of long-COVID syndrome definitions was found. The presence of psychiatric symptoms was evaluated with very different assessment tools.
The most common psychiatric symptoms of the long-COVID syndrome included fatigue, cognitive disturbances/impairment, depression, and anxiety symptoms. The rate of fatigue varied from 93.2–82.3% to 11.5%, cognitive impairment/cognitive dysfunction from 61.4% to 23.5% and depressive-anxiety symptoms from 23.5%to 9.5%
Source: Sampogna G, Di Vincenzo M, Giallonardo V, Perris F, Volpicelli A, Del Vecchio V, Luciano M, Fiorillo A. The Psychiatric Consequences of Long-COVID: A Scoping Review. Journal of Personalized Medicine. 2022; 12(11):1767. https://doi.org/10.3390/jpm12111767  https://www.mdpi.com/2075-4426/12/11/1767/htm (Full text)

Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19

Abstract:

Long Covid — the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) — affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae.

We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days.

Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection.

In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.

Source: Yan XieTaeyoung ChoiZiyad Al-Aly. Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19.

Headache in Post-COVID-19 Patients: Its Characteristics and Relationship with the Quality of Life

Abstract:

Little is known on the characteristics of headaches associated with coronavirus disease 2019 (COVID-19) in Indonesia. The objective of this study was to describe the characteristics of headache in post-COVID-19 patients, and its impact on the patients’ quality of life (QoL), as well as to determine the associated determinants of the poor QoL. A cross-sectional study was conducted in Banda Aceh, Indonesia. The demographic characteristics, clinical symptoms of COVID-19, characteristics of headache, and the QoL were collected and assessed.

Headache was diagnosed and characterized using the International Classification of Headache Disorders, version 3 (ICHD-3). QoL was assessed using a Short Form 36 Health Survey (SF-36) tool. A logistic regression model was used to investigate the associated determinants of poor QoL in post-COVID-19 patients.

A total of 215 post-COVID-19 patients were included in the final analysis, and 21.4% (46/215) of them had a poor QoL due to headache following COVID-19. Those who were unemployed and who contracted COVID-19 less than three months prior to the study had higher odds of having poor QoL compared to those who were employed and who contracted COVID-19 more than three months prior to the study.

Low QoL was also related to headache that occurred less than one month after recovering from COVID-19 (compared to that which occurred longer than one month after); had a high frequency; had a combination sensation of pulsating, pressing, fiery, and stabbing pain; had a high severity score; and had additional symptoms accompanying the headache. In conclusion, headache related to COVID-19 is associated with low QoL among post-COVID-19 patients. A guideline on prevention measures of headache on COVID-19 patients, therefore, needs to be established to avoid long-term consequences.

Source: Mutiawati E, Kusuma HI, Fahriani M, Harapan H, Syahrul S, Musadir N. Headache in Post-COVID-19 Patients: Its Characteristics and Relationship with the Quality of Life. Medicina (Kaunas). 2022 Oct 21;58(10):1500. doi: 10.3390/medicina58101500. PMID: 36295660; PMCID: PMC9609032. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609032/ (Full text)

Psychiatric and neurological complications of long COVID

Abstract:

COVID-19 was primarily considered a pulmonary disease with extrapulmonary manifestations. As the pandemic spread, there has been growing evidence that the disease affects various organs/systems, including the central and peripheral nervous systems. Accumulation of clinical data demonstrates that in a large population of survivors impairments in the function of one or more organs may persist for a long time, a phenomenon commonly known as post COVID or long COVID.

Fatigue and cognitive dysfunction, such as concentration problems, short-term memory deficits, general memory loss, a specific decline in attention, language and praxis abilities, encoding and verbal fluency, impairment of executive functions, and psychomotor coordination, are amongst the most common and debilitating features of neuropsychatric symptoms of post COVID syndrome. Several patients also suffer from compromised sleep, depression, anxiety and post-traumatic stress disorder. Patients with long COVID may demonstrate brain hypometabolism, hypoperfusion of the cerebral cortex and changes in the brain structure and functional connectivity.

Children and adolescents represent a minority of COVID-19 cases, so not surprisingly data on the long-term sequelae after SARS-CoV-2 infections in these age groups are scarce. Although the pathogenesis, clinical characteristics, epidemiology, and risk factors of the acute phase of COVID-19 have been largely explained, these areas are yet to be explored in long COVID. This review aims to provide an update on what is currently known about long COVID effects on mental health.

Source: Zawilska JB, Kuczyńska K. Psychiatric and neurological complications of long COVID. J Psychiatr Res. 2022 Oct 20;156:349-360. doi: 10.1016/j.jpsychires.2022.10.045. Epub ahead of print. PMID: 36326545; PMCID: PMC9582925. https://www.sciencedirect.com/science/article/pii/S0022395622005982 (Full text)

Serological biomarkers of COVID-19 severity at hospital admission are not related to long-term post-COVID pain symptoms in hospitalized COVID-19 survivors

Abstract:

This study investigated the association between serological biomarkers at hospital admission with the development of long-term post-COVID pain symptoms in previously hospitalized coronavirus disease, 2019 (COVID-19) survivors. A cohort study including patients hospitalised because of COVID-19 in 1 urban hospital of Madrid (Spain) during the first wave of the outbreak was conducted. Hospitalisation data, clinical data, and 11 serological biomarkers were collected at hospital admission. Participants were scheduled for an individual telephone interview after hospital discharge for collecting data about post-COVID pain symptoms.

A total of 412 patients (mean age: 62, SD: 15 years; 46.1% women) were assessed twice, at a mean of 6.8 and 13.2 months after discharge. The prevalence of post-COVID pain symptoms was 42.7% (n = 176) and 36.2% (n = 149) at 6.8 and 13.2 months after hospital discharge. Patients reporting post-COVID pain exhibited a greater number of COVID-19-associated symptoms at hospital admission, more medical comorbidities, higher lymphocyte count, and lower glucose and creatine kinase levels (all, P < 0.01) than those not reporting post-COVID pain. The multivariate analysis revealed that lower creatine kinase and glucose levels were significantly associated, but just explaining 6.9% of the variance of experiencing post-COVID pain.

In conclusion, the association between serological biomarkers associated with COVID-19 severity at hospital admission and the development of post-COVID pain is small. Other factors, eg, higher number of COVID-19 onset symptoms (higher symptom load) could be more relevant for the development of post-COVID pain. Because inflammatory biomarkers were not directly analyzed, they may have stronger predictive strengths for the development of post-COVID pain symptoms.

Source: Fernández-de-Las-Peñas C, Ryan-Murua P, de-la-Llave-Rincón AI, Gómez-Mayordomo V, Arendt-Nielsen L, Torres-Macho J. Serological biomarkers of COVID-19 severity at hospital admission are not related to long-term post-COVID pain symptoms in hospitalized COVID-19 survivors. Pain. 2022 Nov 1;163(11):2112-2117. doi: 10.1097/j.pain.0000000000002608. Epub 2022 Feb 3. PMID: 35121694; PMCID: PMC9560903.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560903/ (Full text)

Blood group O is associated with post-COVID-19 syndrome in outpatients with a low comorbidity index

Abstract:

Background: ABO blood group system modulates the inflammatory response and has been implicated in COVID-19. Group O protects against SARS-CoV-2 infection, but there are no data regarding post-COVID-19 syndrome (PCS). Our aim was to assess this possible association.

Methods: Case-control study in a community setting, with subjects who had experienced mild COVID-19. Cases were PCS+, controls were PCS-, and the exposure variable, group O. We collected age, sex, BMI, smoking, comorbidities, inflammatory markers, anti-SARS-CoV-2 IgG antibodies, blood type and clinical data. Five composite inflammatory indices were developed. Multivariate analyses were performed.

Results: We analysed 121 subjects (56.2% women), mean age 45.7 ± 16 years. Blood group frequencies were 41.5%, 7.9%, 5.9%, and 44.5% for A, B, AB and O, respectively. Thirty-six patients were PCS+, without significant differences between cases and controls. Compared to non-O, a higher prevalence of PCS (p = .036), and number of symptoms of PCS (p = .017) were noted in group O. Concerning biomarkers, PCS + and PCS- showed no differences in A, B, and AB groups. In contrast, group O PCS + patients had significantly lower albumin-to-globulin ratio and higher lymphocyte count, fibrinogen, CRP levels, and higher percentages of 3 composite indices, than PCS- subjects. Group O showed a 6-fold increased risk of PCS, compared to non-O (adjusted OR = 6.25 [95%CI, 1.6-23]; p = .007).

Conclusions: Group O has shown a consistent relationship with PCS, characterised by a more intense inflammatory burden than the other blood groups. Blood group O could be part of the immunological link between acute COVID-19 and PCS.

Source: Díaz-Salazar S, Navas R, Sainz-Maza L, Fierro P, Maamar M, Artime A, Basterrechea H, Petitta B, Pini S, Olmos JM, Ramos C, Pariente E, Hernández JL. Blood group O is associated with post-COVID-19 syndrome in outpatients with a low comorbidity index. Infect Dis (Lond). 2022 Dec;54(12):897-908. doi: 10.1080/23744235.2022.2115548. Epub 2022 Aug 27. PMID: 36036090. https://www.tandfonline.com/doi/abs/10.1080/23744235.2022.2115548?journalCode=infd20 (Full text)

Post-COVID-19 syndrome symptoms after mild and moderate SARS-CoV-2 infection

Abstract:

Background: Post-COVID-19 Syndrome (PCS) is characterized by residual symptoms following the initial recovery from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The prevalence of PCS is known to be the highest among severe and critical forms of the disease. However, the occurrence and risk factors for PCS after mild or moderate SARS-CoV-2 infection has not been extensively investigated.

Methods: Online and offline via both paper or mailed questionnaires distributed among Jordan collected between 1st and 21st August 2021, including a total number of 800 respondents, of whom 495 had previous mild to moderate COVID-19 infection. The Newcastle post-COVID syndrome Follow-up Screening Questionnaire was modified, translated, and used as a standard instrument for data collection regarding psychological, medical, and socio-economic symptoms post-infection. The primary outcome was the prevalence of PCS after mild to moderate COVID-19 in Jordan. Secondary outcome was the identification of PCS risk factors.

Results: The most common PCS symptom was mood disturbance followed by fatigue, anxiety, and myalgia. Female gender significantly increased the risk for multiple PCS symptoms. Age < 30 years was found to be an independent risk factor for myalgia (p = 0.001).

Conclusion: PCS is highly prevalent among COVID-19 survivors in Jordan, especially in females and patients with comorbidities. Planning physical and mental rehabilitation services is recommended for those patients with PCS symptoms after mild to moderate COVID-19 infection.

Source: Al-Husinat L, Nusir M, Al-Gharaibeh H, Alomari AA, Smadi MM, Battaglini D, Pelosi P. Post-COVID-19 syndrome symptoms after mild and moderate SARS-CoV-2 infection. Front Med (Lausanne). 2022 Oct 3;9:1017257. doi: 10.3389/fmed.2022.1017257. PMID: 36262270; PMCID: PMC9573938.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9573938/ (Full text)

SARS-CoV-2-on-Chip for Long COVID Management

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a “wicked evil” in this century due to its extended progression and huge human mortalities. Although the diagnosis of SARS-CoV-2 viral infection is made simple and practical by employing reverse transcription polymerase chain reaction (RT-PCR) investigation, the process is costly, complex, time-consuming, and requires experts for testing and the constraints of a laboratory. Therefore, these challenges have raised the paradigm of on-site portable biosensors on a single chip, which reduces human resources and enables remote access to minimize the overwhelming burden on the existing global healthcare sector.

This article reviews the recent advancements in biosensors for long coronavirus disease (COVID) management using a multitude of devices, such as point-of-care biosensors and lab-on-chip biosensors. Furthermore, it details the shift in the paradigm of SARS-CoV-2-on-chip biosensors from the laboratory to on-site detection with intelligent and economical operation, representing near-future diagnostic technologies for public health emergency management.

Source: Cherusseri J, Savio CM, Khalid M, Chaudhary V, Numan A, Varma SJ, Menon A, Kaushik A. SARS-CoV-2-on-Chip for Long COVID Management. Biosensors (Basel). 2022 Oct 18;12(10):890. doi: 10.3390/bios12100890. PMID: 36291027; PMCID: PMC9599615. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599615/ (Full text)

Global prevalence of chronic fatigue syndrome among long COVID-19 patients: A systematic review and meta-analysis

Abstract:

Background: Chronic fatigue syndrome is a persistent and debilitating disorder. According to several studies, chronic fatigue syndrome has been identified among recovered COVID-19 patients as the most common symptom of long COVID. The aim of this systematic review and meta-analysis study was to obtain the prevalence of chronic fatigue syndrome in long COVID cases.

Methods: In this systematic review and meta-analysis, we analysed reported results of studies that assessed the occurrence of chronic fatigue syndrome among COVID-19 patients four weeks after the onset of symptoms. The study selection was commenced by searching PubMed, Web of Science, Science Direct, Scopus, Embase, and Google scholar using the keywords of Chronic fatigue syndrome, COVID-19, and post-COVID-19 syndrome. The searches were without a lower time limit and until April 2022. Heterogeneity of studies was assessed using the I2 index, and a random effects model was used for analysis. Data analysis was performed within the Comprehensive Meta-Analysis software (version 2).

Results: The pooled prevalence of chronic fatigue syndrome four weeks after the onset of COVID-19 symptoms, in 52 studies with a sample size of 127,117, was 45.2% (95% CI: 34.1-56.9%). Meta-regression analysis in examining the effects of the two factors of sample size, and year of study on the changes in the overall prevalence, showed that with increasing sample size, and year of study, the prevalence of chronic fatigue syndrome among long COVID patients (p < 0.05).

Conclusion: Our results show that the overall prevalence of chronic fatigue syndrome as a long COVID symptom is 45.2%. Chronic fatigue after infection with COVID-19 can negatively affect personal and social lives. Given such significant negative consequences caused by the syndrome, it is recommended that health policymakers allocate funds to reduce the adverse effects of this syndrome, by creating programs to support long COVID patients.

Source: Salari N, Khodayari Y, Hosseinian-Far A, Zarei H, Rasoulpoor S, Akbari H, Mohammadi M. Global prevalence of chronic fatigue syndrome among long COVID-19 patients: A systematic review and meta-analysis. Biopsychosoc Med. 2022 Oct 23;16(1):21. doi: 10.1186/s13030-022-00250-5. PMID: 36274177; PMCID: PMC9589726. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589726/ (Full text)

Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics

Abstract:

Background: Brain 18F-FDG PET imaging has the potential to provide an objective assessment of brain involvement in post-COVID-19 conditions but previous studies of heterogeneous patient series yield inconsistent results. The current study aimed to investigate brain 18F-FDG PET findings in a homogeneous series of outpatients with post-COVID-19 conditions and to identify associations with clinical patient characteristics.

Methods: We retrospectively included 28 consecutive outpatients who presented with post-COVID-19 conditions between September 2020 and May 2022 and who satisfied the WHO definition, and had a brain 18F-FDG PET for suspected brain involvement but had not been hospitalized for COVID-19. A voxel-based group comparison with 28 age- and sex-matched healthy controls was performed (p-voxel at 0.005 uncorrected, p-cluster at 0.05 FWE corrected) and identified clusters were correlated with clinical characteristics.

Results: Outpatients with post-COVID-19 conditions exhibited diffuse hypometabolism predominantly involving right frontal and temporal lobes including the orbito-frontal cortex and internal temporal areas. Metabolism in these clusters was inversely correlated with the number of symptoms during the initial infection (r = – 0.44, p = 0.02) and with the duration of symptoms (r = – 0.39, p = 0.04). Asthenia and cardiovascular, digestive, and neurological disorders during the acute phase and asthenia and language disorders during the chronic phase (p ≤ 0.04) were associated with these hypometabolic clusters.

Conclusion: Outpatients with post-COVID-19 conditions exhibited extensive hypometabolic right fronto-temporal clusters. Patients with more numerous symptoms during the initial phase and with a longer duration of symptoms were at higher risk of persistent brain involvement.

Source: Goehringer F, Bruyere A, Doyen M, Bevilacqua S, Charmillon A, Heyer S, Verger A. Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics. Eur J Nucl Med Mol Imaging. 2022 Nov 2. doi: 10.1007/s00259-022-06013-2. Epub ahead of print. PMID: 36322190. https://link.springer.com/article/10.1007/s00259-022-06013-2 (Full text)