COVID-19 Vaccination for the Prevention and Treatment of Long COVID: A Systematic Review and Meta-analysis

Abstract:

Empirical evidence addressing the association between SARS-CoV-2 vaccination and long COVID would guide public health priorities and inform personal health decisions. Herein, the co-primary objectives are to determine the differential risk of long COVID in vaccinated versus unvaccinated patients, and the trajectory of long COVID following vaccination.

Of 2775 articles identified via systematic search, 17 were included, and 6 were meta-analyzed. Meta-analytic results determined that at least one vaccine dose was associated with a protective effect against long COVID (OR 0.539, 95% CI 0.295-0.987, p = 0.045, N= 257 817).

Qualitative analysis revealed that trajectories of pre-existing long COVID following vaccination were mixed, with most patients reporting no changes. The evidence herein supports SARS-CoV-2 vaccination for the prevention of long COVID, and recommends long COVID patients adhere to standard SARS-CoV-2 vaccination schedules.

Source: Ceban F, Kulzhabayeva D, Rodrigues NB, Di Vincenzo JD, Gill H, Subramaniapillai M, Lui LMW, Cao B, Mansur RB, Ho RC, Burke MJ, Rhee TG, Rosenblat JD, McIntyre RS. COVID-19 Vaccination for the Prevention and Treatment of Long COVID: A Systematic Review and Meta-analysis. Brain Behav Immun. 2023 Mar 27:S0889-1591(23)00079-X. doi: 10.1016/j.bbi.2023.03.022. Epub ahead of print. PMID: 36990297; PMCID: PMC10067136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067136/ (Full text)

A prospective cohort study assessing the relationship between long-COVID symptom incidence in COVID-19 patients and COVID-19 vaccination

Abstract:

Current studies about the long-term effects of COVID-19 show a wide range of symptoms. This prospective cohort study aimed to find the incidence of long-COVID symptoms and the associated risk factors.

We followed 669 confirmed COVID-19 patients. Sociodemographic and clinical data were extracted from medical records and collected via semi-structured telephone interviews on days 10, 30, 60, and 90. The incidence of long-COVID symptoms was 41.6% (95% CI 37.8-45.4%). Females [aOR = 1.5 (95% CI 1.1-2.3)], the elderly [aOR = 4.9 (95% CI 2.0-11.3)], and those who required hospitalization [aOR = 5.0 (95% CI 1.3-3.7)] were at a higher risk of developing long-COVID. Patients with dyspnea at day 10 [aOR: 2.4 (95% CI 1.6-3.7] and fatigue at day 60 [aOR: 3.1 (95% CI 1.5-6.3] were also at risk. While non-vaccinated patients were almost seven times more likely to report long-COVID symptoms than vaccinated patients [aOR: 6.9 (95% CI 4.2-11.3)].

In conclusion, long-COVID was common among COVID-19 patients, with higher rates among females, older age groups, hospitalized patients, and those with dyspnea and fatigue, while vaccination provided protection. Interventions should educate health professionals, raise general public awareness about the risks and consequences of Long COVID, and the value of vaccination.

Source: Abu Hamdh B, Nazzal Z. A prospective cohort study assessing the relationship between long-COVID symptom incidence in COVID-19 patients and COVID-19 vaccination. Sci Rep. 2023 Mar 25;13(1):4896. doi: 10.1038/s41598-023-30583-2. PMID: 36966161; PMCID: PMC10039348. https://www.nature.com/articles/s41598-023-30583-2 (Full text)

Risk Factors Associated With Post−COVID-19 Condition A Systematic Review and Meta-analysis

Abstract:

Importance  Post−COVID-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support.

Objective  To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC.

Data sources  Medline and Embase databases were systematically searched from inception to December 5, 2022.

Study Selection  The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients.

Data Extraction and Synthesis  Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023.

Main Outcomes and Measures  The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischemic heart disease; previous hospitalization or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19.

Results  The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalization or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76).

Conclusions and Relevance  This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination.

Trial Registration  PROSPERO Identifier: CRD42022381002

Source: Tsampasian V, Elghazaly H, Chattopadhyay R, et al. Risk Factors Associated With Post−COVID-19 ConditionA Systematic Review and Meta-analysisJAMA Intern Med. Published online March 23, 2023. doi:10.1001/jamainternmed.2023.0750 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2802877 (Full text)

Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people

Abstract:

Objectives: To describe the physical and mental health of children and young people (CYP) 6 months after infection with SARS-CoV-2 and explore whether this varies by COVID-19 vaccination.

Design: A non-hospitalised, national cohort of people aged 11-17 years old with PCR-confirmed SARS-CoV-2 infection and PCR negatives matched at study invitation, by age, sex, region and date of testing who completed questionnaires 6 months after PCR testing. The questionnaire included 21 symptoms and standardised scales (eg, EQ-5D-Y and Chalder Fatigue Scale).

Results: 6407 test-positive and 6542 test-negative CYP completed the 6-month questionnaire: 60.9% of test-positive vs 43.2% of test-negative CYP reported at least one symptom 6 months post-test; 27.6% of test-positive vs 15.9% of test-negative CYP reported 3+ symptoms. Common symptoms at 6 months were tiredness and shortness of breath among both test-positive and test-negative CYP; however, the prevalence of both was higher in test-positive (38.4% and 22.8%, respectively) compared with test-negative CYP (26.7% and 10.9%, respectively). 24.5% test-positive vs 17.8% test-negative CYP met the Delphi research definition of long COVID. Mental health, well-being, fatigue and health-related quality of life scores were similar among test-positive and test-negative CYP 6 months post-test. Similarly, symptomatology was similar among COVID-19-vaccinated and COVID-19-unvaccinated test-positive and test-negative CYP.

Conclusions: Six-months post-PCR testing, CYP who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but test-positive CYP had higher symptom prevalence. Mental health, well-being, fatigue and health-related quality of life were similar among test-positive and test-negative CYP, and symptoms at 6 months were similar in COVID-19 vaccinated and unvaccinated.

Source: Pinto Pereira SM, Nugawela MD, Rojas NK, Shafran R, McOwat K, Simmons R, Ford T, Heyman I, Ladhani SN, Cheung EY, Fox-Smith L, Dalrymple E, Stephenson T. Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people. Arch Dis Child. 2023 Apr;108(4):289-295. doi: 10.1136/archdischild-2022-324656. Epub 2023 Jan 4. PMID: 36599625. https://adc.bmj.com/content/108/4/289.long (Full text)

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)