Epidemiological and clinical perspectives of long COVID syndrome

Abstract:

Long COVID, or post-acute COVID-19 syndrome, is characterized by multi-organ symptoms lasting 2+ months after initial COVID-19 virus infection. This review presents the current state of evidence for long COVID syndrome, including the global public health context, incidence, prevalence, cardiopulmonary sequelae, physical and mental symptoms, recovery time, prognosis, risk factors, rehospitalization rates, and the impact of vaccination on long COVID outcomes. Results are presented by clinically relevant subgroups.

Overall, 10-35% of COVID survivors develop long COVID, with common symptoms including fatigue, dyspnea, chest pain, cough, depression, anxiety, post-traumatic stress disorder, memory loss, and difficulty concentrating. Delineating these issues will be crucial to inform appropriate post-pandemic health policy and protect the health of COVID-19 survivors, including potentially vulnerable or underrepresented groups. Directed to policymakers, health practitioners, and the general public, we provide recommendations and suggest avenues for future research with the larger goal of reducing harms associated with long COVID syndrome.

Source: Huerne K, Filion KB, Grad R, Ernst P, Gershon AS, Eisenberg MJ. Epidemiological and clinical perspectives of long COVID syndrome. Am J Med Open. 2023 Jun;9:100033. doi: 10.1016/j.ajmo.2023.100033. Epub 2023 Jan 18. PMID: 36685609; PMCID: PMC9846887. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846887/ (Full text)

Effect of covid-19 vaccination on long covid: systematic review

Abstract:

Objective To determine the effect of covid-19 vaccination, given before and after acute infection with the SARS-CoV-2 virus, or after a diagnosis of long covid, on the rates and symptoms of long covid.

Design Systematic review.

Data sources PubMed, Embase, and Cochrane covid-19 trials, and Europe PubMed Central (Europe PMC) for preprints, from 1 January 2020 to 3 August 2022.

Eligibility criteria for selecting studies Trials, cohort studies, and case-control studies reporting on patients with long covid and symptoms of long covid, with vaccination before and after infection with the SARS-CoV-2 virus, or after a diagnosis of long covid. Risk of bias was assessed with the ROBINS-I tool.

Results 1645 articles were screened but no randomised controlled trials were found. 16 observational studies from five countries (USA, UK, France, Italy, and the Netherlands) were identified that reported on 614 392 patients. The most common symptoms of long covid that were studied were fatigue, cough, loss of sense of smell, shortness of breath, loss of taste, headache, muscle ache, difficulty sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. 12 studies reported data on vaccination before infection with the SARS-CoV-2 virus, and 10 showed a significant reduction in the incidence of long covid: the odds ratio of developing long covid with one dose of vaccine ranged from 0.22 to 1.03; with two doses, odds ratios were 0.25-1; with three doses, 0.16; and with any dose, 0.48-1.01. Five studies reported on vaccination after infection, with odds ratios of 0.38-0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. The studies failed to adjust for potential confounders, such as other protective behaviours and missing data, thus increasing the risk of bias and decreasing the certainty of evidence to low.

Conclusions Current studies suggest that covid-19 vaccines might have protective and therapeutic effects on long covid. More robust comparative observational studies and trials are needed, however, to clearly determine the effectiveness of vaccines in preventing and treating long covid.

Source: Byambasuren OStehlik PClark J, et al. Effect of covid-19 vaccination on long covid: systematic review

Efficacy of first dose of covid-19 vaccine versus no vaccination on symptoms of patients with long covid: target trial emulation based on ComPaRe e-cohort

Abstract:

Objective To evaluate the effect of covid-19 vaccination on the severity of symptoms in patients with long covid.

Design Target trial emulation based on ComPaRe e-cohort.

Data source ComPaRe long covid cohort, a nationwide e-cohort (ie, a cohort where recruitment and follow-up are performed online) of patients with long covid, in France.

Methods Adult patients (aged ≥18 years) enrolled in the ComPaRe cohort before 1 May 2021 were included in the study if they reported a confirmed or suspected SARS-CoV-2 infection, symptoms persistent for >3 weeks after onset, and at least one symptom attributable to long covid at baseline. Patients who received a first covid-19 vaccine injection were matched with an unvaccinated control group in a 1:1 ratio according to their propensity scores. Number of long covid symptoms, rate of complete remission of long covid, and proportion of patients reporting an unacceptable symptom state at 120 days were recorded.

Results 910 patients were included in the analyses (455 in the vaccinated group and 455 in the control group). By 120 days, vaccination had reduced the number of long covid symptoms (mean 13.0 (standard deviation 9.4) in the vaccinated group v 14.8 (9.8) in the control group; mean difference −1.8, 95% confidence interval −3.0 to −0.5) and doubled the rate of patients in remission (16.6% v 7.5%, hazard ratio 1.93, 95% confidence interval 1.18 to 3.14). Vaccination reduced the effect of long covid on patients’ lives (mean score on the impact tool 24.3 (standard deviation 16.7) v 27.6 (16.7); mean difference −3.3, 95% confidence interval −5.7 to −1.0) and the proportion of patients with an unacceptable symptom state (38.9% v 46.4%, risk difference −7.4%, 95% confidence interval −14.5% to −0.3%). In the vaccinated group, two (0.4%) patients reported serious adverse events requiring admission to hospital.

Conclusion In this study, covid-19 vaccination reduced the severity of symptoms and the effect of long covid on patients’ social, professional, and family lives at 120 days in those with persistent symptoms of infection.

Source: Tran VPerrodeau ESaldanha J, et al. Efficacy of first dose of covid-19 vaccine versus no vaccination on symptoms of patients with long covid: target trial emulation based on ComPaRe e-cohort.

Long COVID: An unpredicted multisystem syndrome of COVID-19 disease

Abstract:

Long COVID is multisystem syndrome with nonspecific symptoms and organic signs of unidentified pathology occurs after COVID-19 disease. Long COVID symptoms has been documented in some cases irrespective of disease severity or hospitalization.
Long COVID symptoms has significant impact on quality of life in those cases suffered from disease in recent past and lingering to almost two years since infection. Importantly, not all cases of COVID-19 were shown long COVID symptoms. Pathophysiology resulting into long COVID manifestations is still not completely validated.
Researchers have reported ‘immune dysregulation’ and ‘coagulation abnormalities’ are probable pathophysiological mechanism for long COVID. Some of the long COVID effects shown complete reversibility including post COVID lung fibrosis. Reboot system to restore immune dysregulation and recovery in long COVID is real concern. Vaccination has not shown significant effect modifying long COVID manifestation. [Editor’s note: See conclusion in full text for a contradictory statement.]
Source: Hital Vishnu Patil, Neel Tandel and Gajanan Godhali. Long COVID: An unpredicted multisystem syndrome of COVID-19 disease. World Journal of Advanced Pharmaceutical and Life Sciences, 2023, 04(01), 005012. https://www.researchgate.net/publication/368757849_Long_COVID_An_unpredicted_multisystem_syndrome_of_COVID-19_disease (Full text)

Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19

Abstract:

Background: The pandemic has highlighted and exacerbated health inequities in both acute coronavirus disease 2019 (COVID-19) and its longer-term sequelae. Given the heterogeneity in definitions of long COVID and the lack of centralized registries of patients with the disease, little is known about the differential prevalence among racial, ethnic, and sex subgroups. This study examines long COVID among Black, White, Asian, and Hispanic Americans and evaluates differences in the associated cognitive symptomology.

Method: Data from four releases of the Census Bureau’s Household Pulse Survey detailing COVID-19 incidence and the duration and type of symptoms among a nationally representative sample of adults from June 1, 2022, through October 17, 2022, were combined. Binary logistic regression assessed the relative likelihood of long COVID among those who had been diagnosed COVID between racial, ethnic, and sex subgroups. Among those reporting long COVID, differences in the prevalence of difficulty understanding and difficulty remembering were assessed. Empirical models accounted for household, regional, vaccination, and insurance differences between respondents. Two-stage selection models were applied to test the robustness of the results.

Results: Among respondents who tested positive for COVID-19, Blacks (OR=1.097, CI=1.034-1.163), females (OR=1.849, CI=1.794-1.907), and Hispanics (OR=1.349, CI=1.286-1.414) were more likely to experience long COVID (symptoms lasting for 3 months or longer) compared to Whites, males, and non-Hispanics respectively. However, those with private health insurance (OR=0.634, CI=0.611-0.658) and who received the COVID vaccine (OR=0.901, CI=0.864-0.94) were less likely to have endured COVID symptoms than their counterparts. Symptoms of long COVID varied significantly between population subgroups. Compared to Whites, Blacks were more likely to have trouble remembering (OR=1.878, CI=1.765-1.808) while Hispanics were more likely to report difficult understanding (OR=1.827, CI=1.413, 2.362). Females, compared to males, were less likely to experience trouble understanding (OR=0.664, CI=0.537, 0.821), but more likely to report trouble remembering (OR=1.34, CI=1.237, 1.451).

Conclusions: Long COVID is more prevalent among Blacks, Hispanics, and females, but each group appears to experience long COVID differently. Therefore, additional research is needed to determine the best method to treat and manage this poorly understood condition.

Source: Jacobs MM, Evans E, Ellis C. Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19. J Natl Med Assoc. 2023 Feb 13:S0027-9684(23)00025-1. doi: 10.1016/j.jnma.2023.01.016. Epub ahead of print. PMID: 36792456; PMCID: PMC9923441. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923441/ (Full text)

Vaccination status and long COVID symptoms in patients discharged from hospital

Abstract:

Effective vaccination against coronavirus mitigates the risk of hospitalisation and mortality; however, it is unclear whether vaccination status influences long COVID symptoms in patients who require hospitalisation. The available evidence is limited to outpatients with mild disease.

Here, we evaluated 412 patients (age: 60 ± 16 years, 65% males) consecutively admitted to two Hospitals in Brazil due to confirmed coronavirus disease 2019 (COVID-19). Compared with patients with complete vaccination (n = 185) before infection or hospitalisation, those with no or incomplete vaccination (n = 227) were younger and had a lower frequency of several comorbidities.

Data during hospitalisation revealed that the no or incomplete vaccination group required more admissions to the intensive care unit (ICU), used more corticosteroids, and had higher rates of pulmonary embolism or deep venous thrombosis than the complete vaccination group. Ninety days after hospital discharge, patients with no or incomplete vaccination presented a higher frequency of symptoms (≥ 1) than patients with complete vaccination (40 vs. 27%; p = 0.013).

After adjusting for confounders, no or incomplete vaccination (odds ratio [OR] 1.819; 95% confidence interval [CI] 1.175-2.815), female sex (OR 2.435; 95% CI 1.575-3.764) and ICU admission during hospitalisation (OR 1.697; 95% CI 1.062-2.712) were independently associated with ≥ 1 symptom 90 days after hospital discharge.

In conclusion, even in patients with severe COVID-19, vaccination mitigates the probability of long COVID symptoms.

Source: Nascimento TCDC, do Valle Costa L, Ruiz AD, Ledo CB, Fernandes VPL, Cardoso LF, Junior JMV, Saretta R, Kalil-Filho R, Drager LF. Vaccination status and long COVID symptoms in patients discharged from hospital. Sci Rep. 2023 Feb 11;13(1):2481. doi: 10.1038/s41598-023-28839-y. PMID: 36774419; PMCID: PMC9922040. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922040/ (Full text)

Long COVID-A New Challenge in Medicine: Focus on Pregnancy and Breastfeeding

Abstract:

Long COVID (coronavirus disease) has been described as a new multi-organ disease, which appears to be more prevalent in women than in men. Pregnant and breastfeeding women are a special subgroup of patients to consider with long COVID, as only scarce data have been collected to date. Menstrual changes are commonly observed during or after COVID-19; some studies also attribute slight changes of cycle length to previous inoculation against the virus.
Pregnant women who have a symptomatic infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are at a higher risk for adverse outcomes and pregnancy-associated complications. Moreover, more and robust data are required to evaluate vertical transmission. COVID vaccines are the most effective tool against the pandemic, as they prevent infection, but also appear to be able to ease long COVID symptoms. Vaccines have been proven safe and effective in both pregnant and breastfeeding women. This article aims to present current data on long COVID in pregnant and breastfeeding women and elucidate risk factors and possible treatment options.
Source: Han E, Gyöngyösi M. [Long COVID-A New Challenge in Medicine: Focus on Pregnancy and Breastfeeding]. Journal fur Gynakologische Endokrinologie (Osterreichische Ausg.). 2023 Feb:1-6. DOI: 10.1007/s41974-023-00250-5. PMID: 36747883; PMCID: PMC9893966. https://europepmc.org/article/med/36747883 (Full text available in German)

Long-COVID Rates Vary Throughout the SARS-CoV-2 Pandemic

Abstract:

The infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) frequently causes a broad range of long-lasting symptoms. This condition, termed long-COVID, influences everyday life of affected individuals in many ways and causes a high economic burden. There is urgent need to obtain better understanding of the risk factors that contribute to the development of long-COVID.

Aim of this study was to investigate the long-COVID rate of supposedly healthy adults during different phases of the pandemic. Therefore, 71,670 blood donations were screened for SARS-CoV-2 total anti-N antibodies between 5 th June 2020 and 30 th November 2022. 351 individuals could be recruited for our study to monitor long-COVID symptoms and their duration. Despite immense worldwide efforts to stop virus dissemination, our data reveal a constantly rising SARS-CoV-2 anti-N seroprevalence rate in Salzburg, Austria, peaking at 84.9% in October 2022.

In addition, our data demonstrate varying rates of long-COVID in the course of the pandemic. While long-COVID rates were about 20% for the time span between March 2020 and August 2021, long-COVID was reported by 12% for infections from September 2021 to August 2022. This could be attributed to different virus variants, but also to increasing vaccination rates. We further found that long-COVID symptoms decline over time: while 18% of our study participants described persisting symptoms 3 months after the seropositive blood donation, 14% reported persisting symptoms 9 months afterwards and 3% after 18 months.

In conclusion, our data reveal that long-COVID symptoms may persist for more than a year after a SARS-CoV-2 infection and that long-COVID rates are varying in the course of the SARS-CoV-2 pandemic.

Source: Nunhofer, et al. Long-COVID Rates Vary Throughout the SARS-CoV-2 Pandemic. Journal of Infectious Diseases & Therapy. Volume 11 • Issue 01 • 1000520. ISSN: 2332-0877.  https://www.researchgate.net/profile/Sandra-Laner-Plamberger/publication/368293143_Long-COVID_Rates_Vary_Throughout_the_SARS-CoV-2_Pandemic/links/63e0dd9062d2a24f920a4d24/Long-COVID-Rates-Vary-Throughout-the-SARS-CoV-2-Pandemic.pdf (Full text)

Impact of COVID-19 vaccination in post-COVID cardiac complications

Abstract:

Background: After the acute infection, COVID-19 can produce cardiac complications as well as long-COVID persistent symptoms. Although vaccination against COVID-19 represented a clear reduction in both mortality and ICU admissions, there is very little information on whether this was accompanied by a decrease in the prevalence of post-COVID cardiac complications. The aim of this study was to analyze the relationship between COVID-19 vaccination and the prevalence of post-COVID cardiac injury assessed by echocardiogram, and long-COVID persistent cardiac symptoms.

Methods: All patients who consulted for post-COVID evaluation 14 days after discharge from acute illness were included. Patients with heart disease were excluded. The relationship between complete vaccination scheme (at least two doses applied with 14 days or more since the last dose) and pathological echocardiographic findings, as well as the relationship of vaccination with persistent long-COVID symptoms, were evaluated by multivariate analysis, adjusting for age, sex and clinical variables that would have shown significant differences in univariate analysis.

Results: From 1883 patients, 1070 patients (56.8%) suffered acute COVID-19 without a complete vaccination scheme. Vaccination was associated with lower prevalence of cardiac injury (1.35% versus 4.11%, adjusted OR 0.33; 95% CI 0.17-0.65, p=0.01). In addition, vaccinated group had a lower prevalence of persistent long-COVID symptoms compared to unvaccinated patients (10.7% versus 18.3%, adjusted OR 0.52; 95% CI 0.40-0.69, p<0.001).

Conclusion: Vaccination against COVID-19 was associated with lower post-COVID cardiac complications and symptoms, reinforcing the importance of fully vaccinating the population.

Source: Parodi JB, Indavere A, Bobadilla Jacob P, Toledo GC, Micali RG, Waisman G, Masson W, Epstein ED, Huerin MS. Impact of COVID-19 vaccination in post-COVID cardiac complications. Vaccine. 2023 Feb 17;41(8):1524-1528. doi: 10.1016/j.vaccine.2023.01.052. Epub 2023 Jan 27. PMID: 36725436; PMCID: PMC9885297. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885297/ (Full text)

Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis

Abstract:

Background: The relationship between coronavirus disease 2019 (COVID-19) vaccination and long COVID has not been firmly established. We conducted a systematic review and meta-analysis to evaluate the association between COVID-19 vaccination and long COVID.

Methods: PubMed and EMBASE databases were searched on September 2022 without language restrictions (CRD42022360399) to identify prospective trials and observational studies comparing patients with and without vaccination before severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We also included studies reporting symptomatic changes of ongoing long COVID following vaccination among those with a history of SARS-CoV-2 infection. Odds ratios (ORs) for each outcome were synthesized using a random-effects model. Symptomatic changes after vaccination were synthesized by a one-group meta-analysis.

Results: Six observational studies involving 536,291 unvaccinated and 84,603 vaccinated (before SARS-CoV-2 infection) patients (mean age, 41.2-66.6; female, 9.0-67.3%) and six observational studies involving 8,199 long COVID patients (mean age, 40.0 to 53.5; female, 22.2-85.9%) who received vaccination after SARS-CoV-2 infection were included. Two-dose vaccination was associated with a lower risk of long COVID compared to no vaccination (OR, 0.64; 95% confidence interval [CI], 0.45-0.92) and one-dose vaccination (OR, 0.60; 95% CI, 0.43-0.83). Two-dose vaccination compared to no vaccination was associated with a lower risk of persistent fatigue (OR, 0.62; 95% CI, 0.41-0.93) and pulmonary disorder (OR, 0.50; 95% CI, 0.47-0.52). Among those with ongoing long COVID symptoms, 54.4% (95% CI, 34.3-73.1%) did not report symptomatic changes following vaccination, while 20.3% (95% CI, 8.1-42.4%) experienced symptomatic improvement after two weeks to six months of COVID-19 vaccination.

Conclusions: COVID-19 vaccination before SARS-CoV-2 infection was associated with a lower risk of long COVID, while most of those with ongoing long COVID did not experience symptomatic changes following vaccination.

Source: Watanabe A, Iwagami M, Yasuhara J, Takagi H, Kuno T. Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis. Vaccine. 2023 Feb 8:S0264-410X(23)00134-2. doi: 10.1016/j.vaccine.2023.02.008. Epub ahead of print. PMID: 36774332; PMCID: PMC9905096. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905096/ (Full text)