Abstract
Objective: To investigate the pattern and prevalence of persistent symptoms of Post-COVID-19 Syndrome (PCS) at 3, 6, 9, and 18 months after discharge. Associated risk factors were further examined to potentially explain the persistence of these symptoms.
Design and Setting: A cross-sectional cohort study was conducted at the primary health care facility of Aruba, Dr. Horacio E. Oduber Hospital (HOH).
Participants: Inclusion criteria were adults hospitalized at HOH for at least one night between March and July 2021 and laboratory-confirmed COVID-19 diagnosis. Exclusion criteria were deceased before the follow-up, not able to mobilize before or after discharge, living outside of Aruba or in nursing homes, and patients with psychosis, dementia, or hospitalized due to unrelated diseases.
Methods: Eligible and willing participants completed a 20-question survey: a self-reported symptoms questionnaire about symptoms during and after COVID-19 infection, level of dyspnea measurement (mMRC-scale), quality of life measurement (EQ-5D-5E with EuroQoL VAS), and mental well-being (WHO-5). Hospitalization related data were gathered via retrospective analysis of patient records. Chi-square test, logistic regression, and ANOVA analyses were conducted; P<0.05 was chosen as level of statistical significance for all analyses.
Results: In total, 222 (34.5%) patients were eligible, consenting, and completed the survey. Most participants were interviewed a year or more after their initial COVID-19 infection. Fatigue (37.8%), new-onset dyspnea (38.7%), hair loss (20.3%), and muscle pain (18.0%) were the most frequently reported symptoms at any time post COVID-19 infection. Female participants were found more likely to experience fatigue (P<0.05, OR 2.135, 95% CI 1.154-3.949) and new-onset dyspnea (P<0.05, OR 2.026 95% CI 1.093-3.756) after initial infection. Participants with one or more respiratory comorbidity were more likely to experience new-onset dyspnea (P<0.05, OR 2.681, 95% CI 1.223-5.873). None of the predictor variables was associated with cognitive impairment.
Conclusion: This study identified female sex and respiratory comorbidity as crucial risk factors for PCS. Females were also found to have significantly lower health scores. Female participants were more likely to experience fatigue and dyspnea after COVID-19 infection.
It has been 3 years since the first detection of the SARS-COV-2 virus in Wuhan and the subsequent Coronavirus 19 (COVID-19) disease pandemic.1 Yet, health systems around the world continue to struggle with the aftermath of the pandemic, the ongoing resurgence of acute COVID-19 infections, and the increasing number of people requiring long-term support for post-COVID-19 symptoms.
This phenomenon, termed the Post-COVID-19 Syndrome (PCS), is defined by the World Health Organization (WHO) as a condition occurring in individuals with a history of SARS-CoV-2 infection, usually 3 months from the initial onset of symptoms and lasting at least 2 months, which cannot be explained by an alternative diagnosis. Common symptoms include fatigue, dyspnea, and cognitive dysfunction, among others.2 Since the early months of the pandemic, there has been a rising awareness among COVID-19 survivors about its long-term sequelae 2. However, due to the acuity of the crisis and the need for research on the acute disease presentation and potential treatments, long COVID (as termed by patients) was not recognized by the scientific community until months later.3 Still, the full extent of PCS is not entirely understood, and exploration of the burden of the disease is needed. There is a necessity for long-term follow-up studies in different contexts to explore the pattern of persistent symptoms and associated protective and exacerbating factors.
Furthermore currently published studies are predominantly in European, North American, or Southeast Asian contexts, despite Latin America and the Caribbean being most severely affected globally by the pandemic.4 In light of this recognition and the obvious burden of disease on fragile health systems in Latin America, to date very few publications highlight the impact of long COVID in the region.5 Available literature, with follow up mostly of 6 months, reports the prevalence of long-term sequalae among hospitalized patients is reported at 31%–87%.6-8 This number was lower among outpatient populations, ranging from 24% to 55%.9 While these studies are significant contributions to the understanding of PCS, it is hypothesized that COVID-19 patients have relevant clinical symptoms beyond this cut-off, affecting their physical and mental well-being.
The purpose of this study was to investigate the pattern and prevalence of persistent PCS symptoms among adults hospitalized with the SARS-COV-2 virus in the primary health care facility of Aruba, Dr. Horacio E. Oduber Hospital (HOH). Additionally we wanted to explore the associated risk factors in these patients, which could potentially explain the persistence of these symptoms. This article reports on the initial review of the collected data, focusing on the long COVID disease presentation on Aruba and identifying initial risk factors.
Methods
Study Design and Population
To gather comprehensive data on PCS in Aruba, we used several different research approaches that included retrospective data analysis of hospital medical records and a survey of the severity of symptoms during COVID-19 and at the measurement moment.
Inclusion criteria were adults (age >18 years) hospitalized at HOH for at least one night between March 1, 2020, and July 30, 2021, laboratory-confirmed COVID-19 diagnosis, speak Papiamento, English, Dutch, or Spanish. Exclusion criteria were not given informed consent, deceased before the follow-up, not able to mobilize before or after discharge, could not be contacted, living outside of Aruba or in nursing homes, and patients with psychosis, dementia, or hospitalized due to unrelated diseases.
As of July 30, 2021, 760 were hospitalized in HOH due to COVID-19 and, if eligible, were included in the database survey. Selected research team members (MF, JDK, CB, and SK) called the identified potential participants between August and December 2021 to obtain their verbal consent, assess their eligibility, and conduct the survey. There is no randomization in a cohort study.
Out of 643 initially identified eligible participants, 367 surveys were collected by a trained team member, of which 11 were deceased, 24 were in a nursing home, 7 were incapacitated, 29 were living abroad, 13 were not adults, 27 were on the list twice, 6 were currently admitted, 2 did not give consent, 20 were unable to be contacted, and 6 were excluded for an unspecified reason. The analysis included 222 patients who completed the phone survey and had full medical dossier data.
Instruments
This study is the first report from a more extensive study with a broader research question. Eligible and willing participants completed a 20-question survey comprising four parts: (1) a self-reported symptoms questionnaire about newly occurring and persisting symptoms post-COVID-19 infection; (2) level of dyspnea measurement using the mMRC-scale;10 (3) the EQ-5D-5E questionnaire and the EuroQoL visual analog scale for quality of life;11 and (4) measuring mental well-being using the WHO Five Well-Being Index.12 The survey was validated using two rounds of Delphi consensus with a panel consisting of two pulmonologists and an internist-infectious diseases specialist. Due to the nature of the study, there is no blinding of the patients or researchers. Patient files were anonymized by coding. To accelerate data collection, medical data were extracted from hospital records by one trained researched (VD) simultaneously to survey collection. The researcher received previously defined variables, which were then manually extracted. Missing data were kept track of, and patients with insufficient data on record were excluded (Figure 1).
Flowchart study participants. From the initially identified 761 potential participants, the deaceased were excluded. A silmutaneous data collection from medical dossiers and surveys took place. Once survey phase was completed, the data was merged resulting in 222 inclusions for analysis.
In this report, only the results of the symptom questionnaire were used to sufficiently answer the research question and study objectives. The four different tools used in the survey allow for a relatively quick assessment of the well-being of patients at the start of the study. Comorbidities were identified with the retrospective analysis of patient records and corroborated with the self-reported survey.
Statistical Analysis
The surveys of eligible and willing participants were collected verbally, and the responses were noted by the interviews on paper and filled in on Survey Monkey. Identified sample size for the prevalence of 80% of at least one PCS symptom is 241 (P ≤ 0.5, CI 95%). However, since the population is limited to the number of hospitalized patients, this power analysis has little additive value.
Covariates
Associated factors focused on in this study were age, sex, body mass index (BMI), comorbidities (reported in the following categories: diabetes, hypertension, obesity, chronic kidney disease, chronic liver disease, HIV/AIDS, mental health issues, malignancies, respiratory, cardiovascular, and rheumatologic/immune conditions), and severity of illness (admission to ICU). For ease of analysis, age and BMI were divided into categories in increments of 10. Additionally, age was analyzed separately in two groups of 60 and younger and older than 60. For the purpose of reflecting participants health status, the sum of comorbidities was used. In further analysis, we specifically focused on diabetes and respiratory conditions as comorbidities.
Outcomes
Participants were asked if they experienced specific symptoms [Appendix 1. Full questionnaire (available online)] first at the time of initial COVID-19 infection and which of these symptoms were still present (at the point of interview). Based on the date of the first positive COVID PCR test, each patient was grouped in the 3, 6, 12, or 18-month category in relation to the date of the survey. This study used the PCS definition by WHO2 as the outcome (fatigue, dyspnea, cognitive impairment) and the EuroQoL visual analog scale for quality of life. Based on the WHO definition, we created PCS as an outcome, which included patients who experienced both fatigue and dyspnea. Cognitive impairment was excluded due to the low number of patients reporting it.
The associations between continuous variables were described as mean with standard deviation (SD). Categorical variables were expressed as a percentage and compared using the Chi-square test. The significance of correlations was indicated by a correlation test inferring Pearson correlation with alpha=0.05. Logistic regression was used to examine the relationship between the independent covariates for the presence of fatigue, dyspnea, and cognitive impairment at 3, 6, 12, and 18-months post-COVID-19 infection. Results are reported as odds ratio (OR) with a 95% confidence interval (CI). Logistic regression analysis was used to study the independent covariates for the presence of fatigue, dyspnea and cognitive impairment at 3, 6, 12 and 18-months post-hospital admission. We chose ≤ 0.05 as level of statistical significance for all analyses. To understand the association of sex and age on health score, ANOVA analysis was conducted. Statistical analyses were performed using IBM SPSS Version 28.0.
Ethics Approval
Verbal informed consent was asked before enrolment in the study. In addition, data from the participant were recorded in a case record, and all answers from the respondents were treated discretely and anonymously by coded case records. The Dr. Horacio E. Oduber Hospital ethics committee approved the proposal (METC_230321).
Results
In total, 222 (34.5%) of the initially identified 643 patients hospitalized with COVID-19 at HOH were eligible, consented, and completed the survey. The population ranged widely in age, between 29 and 83 years, with a mean BMI of 33.9 ± 9.3 kg/m2. In addition, 82.9% of the study population had at least one comorbidity, and over half were of American Caribbean (predominantly Aruban) ethnicity. Most participants were interviewed a year or more after their initial COVID-19 infection (100 and 79, at 12 and 18 months, respectively), with smaller groups at 6 and 3 months (30 and 13, respectively). Population characteristics are listed in Table 1.
Demographic characteristics of the study population (N=222) at the point of survey collection
Symptoms During and Post-COVID-19 Infection
Participants were asked, first, to recall their symptoms during the initial COVID-19 illness. Most common complaints were new-onset dyspnea (83.3%), fever (81.1%), fatigue (70.7%), new-onset cough (58.1%), and loss of taste and or smell (50%, Table 2). Further, the participants were asked about their residual symptoms at the point of the survey (Table 2); 32.9% of the participants reported no persistent symptoms post-COVID-19, while 14.9%, 18.0%, 10.4%, 7.2%, and 16.7% reported one, two, three, four, and five or more symptoms, respectively. Fatigue (37.8%), new-onset dyspnea (38.7%), hair loss (20.3%), and muscle pain (18.0%) were the most frequently reported symptoms. These also matched when stratified according to times of survey collection, with an outlier of mucus production (15.4%) at 3 months post-COVID-19 illness (Table 2).
Prevalence of COVID-19 symptoms at the point of infection and at point of survey collection
Predictive Factors
Identified potential predictive factors were first analyzed to determine if they have a non-random association with earlier defined outcomes. We found that relationships between ICU, diabetes, and the outcomes were due to chance and not statistically significant. No further tests were performed on those factors. Fatigue was significantly associated with sex, age, BMI, respiratory comorbidities, and a cumulative number of comorbidities (Table 3). Dyspnea was associated (P≤0.05) with sex, age, and respiratory comorbidity (Table 3). Further multivariate analysis was performed using logistic regression to understand the observed associations better. Female participants were found to be more likely to experience fatigue (P≤0.05, OR 2.135, 95% CI 1.154-3.949) and dyspnea (P≤0.05, OR 2.026 95% CI 1.093-3.756). Participants with one or more respiratory comorbidity were found to be more likely to experience new-onset dyspnea (P≤0.05, OR 2.681, 95% CI 1.223-5.873). None of the predictor variables were associated with cognitive impairment (Table 3).
Multivariate analysis of predictors of PCS using logistic regression and Chi-Square.
To further unpack the gender association, stratified (age ≤60 years or >60 years) analysis was conducted. Chi-square analysis and multivariate logistic regression showed that females were more likely to experience dyspnea (P<0.05, OR 2.597, 95% CI 1.164-5.729) and fatigue (P<0.05, OR 3.115, 95% CI 1.367-7.099) in the ≤60 age group but not in the >60 age group. According to the stratified chi-square results (P<0.05), respiratory comorbidity was also found to be associated with dyspnea and fatigue in the >60 age group and with dyspnea in the ≤60 age group. However, after running a multivariate analysis, this effect disappeared (Table 4).
Multivariate analysis of predictors of PCS using logistic regression and Chi-Square, stratified by age.
Health Score and Post-COVID Syndrome
Participants were asked to give a subjective score to categorize their overall health at the point of the interview on a scale of 0-100 (EQ-VAS), the Health Scores.9 This score allows one to gain insight into a patient’s perspective, and higher scores indicate a better perception of one’s health status. The mean score reported by study participants was 79.6 ± 14.5 and ranged between 40 and 100. Further analysis showed a significant association between gender and health score, with females scoring lower than men (P=0.003). Age also has an association with health score (P=0.042); however, it is not a linear relationship as the middle-aged patients (ages 36-55) scored lower than young patients (ages 26-35) and older patients (ages 56-75) (Table 5).
Results of the association between sex, age category and health score (ANOVA table)
To define the prevalence of long COVID in the population we used two approaches. First, as defined by WHO, the PCS is present in 27.9% of study participants; according to this definition, most participants are reporting PCS at 18 months with 35.4% (Table 2). Second, 67.1% of participants experienced one or more symptom at the point of interview. Looking at the mean number of symptoms reported, the cumulative number of symptoms trends upwards with time, since the COVID-19 infection, with a peak at 12 months. Concurrently, the self-reported health score is getting lower between 3 and 12 months follow up (85.75 ± 8.433 to 76.85 ± 14.430) and slightly improved at 18 months post. Interestingly, the mental health score improved with time. The relationship between mental health, health score, and long COVID will be further explored in the future.
Discussion
Long COVID prevalence varies considerably based on the study population, study power, or other factors. We estimate that two in three people hospitalized with COVID-19 in Aruba will experience at least one persistent symptom at least 3 months post-discharge. The high prevalence could be related to the fact that this population only included patients with moderate COVID-19 disease, which required hospitalization. Notably, fatigue and dyspnea symptoms were supported by all PCS studies as the most common symptoms.1,2,6-9,13-19 A more recent, large meta-analysis reveals a much lower prevalence (6.2%) of PCS symptoms amongst COVID-19 survivors. When separated into groups based on disease severity, the reported long COVID prevalence was 5.7% for not hospitalized patients, 27.5% for patients admitted to the hospital, and 43.1% admitted to ICU.16 Their findings of hospitalized patients are similar to the PCS prevalence we identified based on the WHO case definition (27.9%).
Interestingly, ICU stay was not a predictive factor in this population, while many studies reported that it as a risk factor.1,8,16 It is unclear if this difference is due to the relatively small sample size in our study. One of the authors recalled that due to the small number of ICU beds at the HOH, many patients were unable to be admitted to the ICU, even though there were indications for it. Although we cannot corroborate this observation, as there are no records of people who should have been in the ICU but were not admitted, it could partly explain ICU not as a predictive factor in this population. There may be other factors involved, such as physiotherapy. Typically ICU patients will receive more support than other hospitalized patients, including post hospitalization. Surprisingly, rehabilitation has not been proven to universally improve long COVID outcomes.9
Our study is one of the first to look at PCS up to 18 months post-diagnosis, and fatigue remains the most common reported PCS symptom.1,6,7,13,17,24,25 Studies with short follow up report 65.3% of patients not feeling physically or mentally like before the illness,13 and that the persistence of symptoms has an important impact on general, physical, and mental health status, social functioning, and quality of life within 35 days of discharge.25 Based on the Health Score and the Well-Being Index, it appears the subjective experience of quality of life are worst in the first year after acute illness, with some improvement by 18 months. Whether this improvement can be attributed to improvement of symptoms (evidence points to a decrease in reported symptoms), or better symptom management resulting in better quality of life, or another factor is unclear. The few studies with 18 month follow-up do report impaired daily life activities due to persistent symptoms at the end of their follow-up period.26,27
The results further exemplify the significance of PCS in the COVID-19 survivors, as millions of people around the world will experience a number of symptoms, some will require medical attention and treatment. Most common symptoms of long COVID, specifically fatigue, joint pain, muscle pain, and cognitive impairment, resemble post-infectious fatigue syndrome (PIFS; also known as myalgic encephalomyelitis). PIFS is a collection of symptoms related to chronic fatigue syndrome (CFS), with a causative infectious (usually viral) agent.20 Emerging research has been linking PCS to this phenomenon due to the extensive symptom resemblance,6,9,21,22 both with unclear underlying pathophysiology, which may be shared. This resemblance creates avenues for further research and drug repurposing for long COVID treatment.9 There are some apparent differences between PIFS and PCS, as PCS involves many systems–lungs, heart, brain, kidney, liver, and gastrointestinal tract,23 which are not typically affected in PIFS. Particularly, dyspnea is a rare symptom in PIFS, but it is a very common symptom of long COVID.9 The most significant barrier to understanding long COVID is the lack of data on follow-up post-6 months, as we are still awaiting results from long-term cohorts.22
The relationship between sex and long COVID is not fully understood yet, but many studies report it as significant.7,9,16,18 Interestingly male sex is a predictor of worse COVID-19 acute infection and death,28 while women experience less severe disease and better antibody responses.16 The gender disparity of long COVID could be attributed to survivor bias or pathophysiology. The current understanding of PSC etiology is related to residual inflammation, organ damage, non-specific effects from hospitalization or prolonged ventilation, social isolation, or disease impact on pre-existing health conditions. It is hypothesized that the immune dysregulation and persistence of inflammatory reaction contributes to an immunocompromised state, which together with secondary stress can lead to development of long COVID.14,16,29 Other studies reported older age, high symptom load during initial infection, hospitalization, and comorbidities, particularly asthma, as predisposing factors.9,14
The setting of a hospital servicing the small Caribbean Island of Aruba is unique and adds to COVID-19 research in Latin America and the Caribbean. Our results are being compared to studies in predominantly European, North American, or Asian settings with populations difficult to compare to Aruba.6,7,9,16-18 A UK study did include ethnicity in the demographic questionnaire, reporting 8.4%-15.8% Hispanic/Latinos, and found that “White and non-white patients were equally affected”.8 Our study population comprised 53.6% of people identifying as American Caribbeans and 18.5% Hispanic/Latino. PubMed results on long COVID in the region are scarce. Only one study from the Latin America region at the time of submission, a prospective cohort study from Brazil, found that 80% of participants were experiencing long COVID symptoms 120 days or more post-acute disease onset, most commonly reporting fatigue, dyspnea, cough, headache, and loss of overall muscle strength.30 The lack of data in the region makes it difficult to come to conclusions; however, this evidence points to a potential link between race and higher PSC prevalence.31
The importance of social and economic determinants is well documented with respect to health outcomes, particularly in settings where the systems have been set up by a colonial power. It is no surprise that social inequities, lack of social protection, and economic inequalities have been linked to complications in COVID-19 management, which can be further complicated by environmental factors (pollution, climate, chemical exposure, and built environment).23 In a critical letter, Sakhamuri et al.3 shed light on a continuing crisis in the Latin American and Caribbean region, worsened by an unprecedented economic decline. Authors estimate more than 29 million people are suffering from long COVID and need or will need various means of support. Our study contributes to the small sample of studies in the region, although more research is required to manage the disabling effects of PCS and explore the risk factors, etiology, prevention, diagnosis, and treatment of long COVID, which has the potential to spark a second public health crisis after the pandemic itself. Therefore, proactive efforts to identify the hallmarks of this heterogeneous condition are necessary for a rigorous scientific effort to investigate and mitigate this threat.
Limitations
It is important to acknowledge the small sample size of this study, as it focused only on hospitalized patients at HOH in Aruba, further limiting the study population to only people with moderate to severe COVID-19 infection. This impacted the sample size as it was finite, based on the people who were hospitalized due to COVID-19 on an island with a population of 106,500. Furthermore, the small sample of our population limited the power of our findings. However, we believe that the importance of reporting long COVID in the Latin American and Caribbean region outweighs this shortcoming and draws more attention to this new emerging patient population.
The questionnaire aimed to be as complete as possible, however as it was created in August 2021, there was limited data on which symptoms are relevant, thus omitting or simplifying now recognized important outcomes, for example making distinctions in “cognitive impairment”, such as “memory issues”, “brain fog”, or “difficulty sleeping”. The questionnaire was collected once per each participant, due to the limited time of the researchers, resulting in no longitudinal data. This method of sampling carries the risk of recall bias specifically for the symptoms during the initial COVID-19 infection. The PCS symptoms are at point of survey which do not fall to the same shortcoming.
Since the early stages of the pandemic, it became obvious that COVID-19 pandemic will have long term consequences on the healthcare systems but also on the individual level. The herculean task of collecting all the medical records data and collect all surveys among all admitted patients was carried out by a small research team of five people, consisting primarily of front line physicians. This research was conducted with little funding and, at the time of data collection, little support for longitudinal data collection – or any data collection. Coming from a Small Island setting, it’s not hard to imagine that this barrier is impeding if not completely stopping any research, and especially COVID-19 related research. Especially considering the high burden of COVID-19 in Latin America and Caribbean where the priorities are on sustaining fragile health care systems and delivering sufficient healthcare in the midst of a crisis.
Conclusion
This cross-sectional cohort study of Post-COVID-19 Syndrome in Aruba provides insight into the prevalence of the persistent symptoms of COVID-19 patients between 3 and 18 months post-hospitalization and the associated risk factors. The identified frequent symptoms of long COVID are fatigue, muscle pain, new-onset dyspnea, and hair loss, and they conform to the literature, which shows 67.1 % of participants experience one or more persistent symptoms post-acute infection. This study identified female sex and respiratory comorbidity as crucial risk factors for PCS. Females were also found to have significantly lower health scores. Female participants were more likely to experience fatigue and dyspnea post-COVID-19 infection. There is a need for long-term research into COVID-19 patients to understand the implications and consequences of the persistent symptoms better.
Acknowledgements
The authors would like to acknowledge and thank Noëlia Khalil, Cindy van der Linde and Melanie Figaroa for their help in gathering survey data as part of this research.
Footnotes
Disclosure: The authors have no conflicts of interest or financial support related to this work to report.
- Received December 14, 2022.
- Revision received April 12, 2023.
- Accepted May 4, 2023.
References
- 1.↵Huang C, Huang L, Wang Y, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232. doi:10.1016/S0140-6736(20)32656-8.
- 2.↵Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV; WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e107. doi:10.1016/S1473-3099(21)00703-9.
- 3.↵Callard F, Perego E. How and why patients made Long Covid. Soc Sci Med. 2021;268:113426. doi:10.1016/j.socscimed.2020.113426.
- 4.↵Sakhamuri SM, Jankie S, Pinto Pereira LM. Calling on Latin America and the Caribbean countries to recognise the disability from long COVID. Lancet Reg Health Am. 2022;15:100362. doi:10.1016/j.lana.2022.100362
- 5.↵Alvarez-Moreno CA, Pineda J, Bareño A, Espitia R, Rengifo P. Long COVID-19 in Latin America: Low prevalence, high resilience or low surveillance and difficulties accessing health care? Travel Med Infect Dis. 2023;51:102492. doi:10.1016/j.tmaid.2022.102492.
- 6.↵Lopez-Leon S, Wegman-Ostrosky T, Perelman C, More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep. 2021;11(1):16144. doi:10.1038/s41598-021-95565-8
- 7.↵Aiyegbusi OL, Hughes SE, Turner G, ; TLC Study Group. Symptoms, complications and management of long COVID: a review. J R Soc Med. 2021;114(9):428-442. doi:10.1177/01410768211032850. Medline
- 8.↵Taquet M, Dercon Q, Luciano S, Geddes JR, Husain M, Harrison PJ. Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19. PLoS Med. 2021;18(9):e1003773. doi:10.1371/journal.pmed.1003773.
- 9.↵Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 2021;53(10):737-754. doi:10.1080/23744235.2021.1924397
- 10.↵Mahler DA, Wells CK. Evaluation of clinical methods for rating dyspnea. Chest. 1988;93(3):580-586. doi:10.1378/chest.93.3.580.
- 11.↵Feng YS, Kohlmann T, Janssen MF, Buchholz I. Psychometric properties of the EQ-5D-5L: a systematic review of the literature. Qual Life Res. 2021;30(3):647-673. doi:10.1007/s11136-020-02688-y.
- 12.↵Topp CW, Østergaard SD, Søndergaard S, Bech P. The WHO-5 Well-Being Index: a systematic review of the literature. Psychother Psychosom. 2015;84(3):167-176. doi:10.1159/000376585.
- 13.↵Bastola A, Nepal R, Shrestha B, Persistent Symptoms in Post-COVID-19 Patients Attending Follow-Up OPD at Sukraraj Tropical and Infectious Disease Hospital (STIDH), Kathmandu, Nepal. Trop Med Infect Dis. 2021;6(3):113. doi:10.3390/tropicalmed6030113
- 14.↵Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, Welson NN. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J. 2022;19(1):158. doi:10.1186/s12985-022-01891-2
- 15.Caspersen IH, Magnus P, Trogstad L. Excess risk and clusters of symptoms after COVID-19 in a large Norwegian cohort. Eur J Epidemiol. 2022;37(5):539-548. doi:10.1007/s10654-022-00847-8.
- 16.↵Global Burden of Disease Long COVID Collaborators, Wulf Hanson S, Abbafati C, Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021. JAMA. 2022;328(16):1604-1615. doi:10.1001/jama.2022.18931
- 17.↵Maestre-Muñiz MM, Arias Á, Mata-Vázquez E, Long-Term Outcomes of Patients with Coronavirus Disease 2019 at One Year after Hospital Discharge. J Clin Med. 2021;10(13):2945. doi:10.3390/jcm10132945.
- 18.↵Seeßle J, Waterboer T, Hippchen T, Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study. Clin Infect Dis. 2022;74(7):1191-1198. doi:10.1093/cid/ciab611.
- 19.↵Whitaker M, Elliott J, Chadeau-Hyam M, Persistent COVID-19 symptoms in a community study of 606,434 people in England. Nat Commun. 2022;13(1):1957. doi:10.1038/s41467-022-29521-z.
- 20.↵Stormorken E, Jason LA, Kirkevold M. Factors impacting the illness trajectory of post-infectious fatigue syndrome: a qualitative study of adults’ experiences. BMC Public Health. 2017;17(1):952. doi:10.1186/s12889-017-4968-2.
- 21.↵Sandler CX, Wyller VBB, Moss-Morris R, Long COVID and Post-infective Fatigue Syndrome: A Review. Open Forum Infect Dis. 2021;8(10):ofab440. doi:10.1093/ofid/ofab440.
- 22.↵Wong TL, Weitzer DJ. Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology. Medicina (Kaunas). 2021;57(5):418. doi:10.3390/medicina57050418
- 23.↵Chavda VP, Vuppu S, Mishra T, Recent review of COVID-19 management: diagnosis, treatment and vaccination. Pharmacol Rep. 2022;74(6):1120-1148. doi:10.1007/s43440-022-00425-5.
- 24.↵Nalbandian A, Sehgal K, Gupta A, Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615. doi:10.1038/s41591-021-01283-z.
- 25.↵Jacobs LG, Gourna Paleoudis E, Lesky-Di Bari D, Persistence of symptoms and quality of life at 35 days after hospitalization for COVID-19 infection. PLoS One. 2020;15(12):e0243882. doi:10.1371/journal.pone.0243882.
- 26.↵Demko ZO, Yu T, Mullapudi SK, Post-acute sequelae of SARS-CoV-2 (PASC) impact quality of life at 6, 12 and 18 months post-infection. Preprint. medRxiv. 2022;2022.08.08.22278543. doi:10.1101/2022.08.08.22278543
- 27.↵Hastie CE, Lowe DJ, McAuley A, Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study [published correction appears in Nat Commun. 2022 Nov 1;13(1):6540]. Nat Commun. 2022;13(1):5663. doi:10.1038/s41467-022-33415-5
- 28.↵Marik PE, DePerrior SE, Ahmad Q, Dodani S. Gender-based disparities in COVID-19 patient outcomes. J Investig Med. 2021;69(4):814-818. doi:10.1136/jim-2020-001641.
- 29.↵Büttiker P, Stefano GB, Weissenberger S, HIV, HSV, SARS-CoV-2 and Ebola Share Long-Term Neuropsychiatric Sequelae. Neuropsychiatr Dis Treat. 2022;18:2229-2237. doi:10.2147/NDT.S382308
- 30.↵Bonifácio LP, Csizmar VNF, Barbosa-Júnior F, Long-Term Symptoms among COVID-19 Survivors in Prospective Cohort Study, Brazil. Emerg Infect Dis. 2022;28(3):730-733. doi:10.3201/eid2803.212020
- 31.↵Magesh S, John D, Li WT, Disparities in COVID-19 Outcomes by Race, Ethnicity, and Socioeconomic Status: A Systematic-Review and Meta-analysis [published correction appears in JAMA Netw Open. 2021 Dec 1;4(12):e2144237] [published correction appears in JAMA Netw Open. 2022 Feb 1;5(2):e222170]. JAMA Netw Open. 2021;4(11):e2134147. doi:10.1001/jamanetworkopen.2021.34147
