key: cord-0737534-sh0el5k0
authors: Malik, Preeti; Patel, Karan; Pinto, Candida; Jaiswal, Richa; Tirupathi, Raghavendra; Pillai, Shreejith; Patel, Urvish
title: Post‐acute COVID‐19 syndrome (PCS) and health‐related quality of life (HRQoL)—A systematic review and meta‐analysis
date: 2021-09-07
journal: J Med Virol
DOI: 10.1002/jmv.27309
sha: 38a2d6b455b4cca80aec3756d94312d04bf41a11
doc_id: 737534
cord_uid: sh0el5k0

There is an established literature on the symptoms and complications of COVID‐19 but the after‐effects of COVID‐19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post‐acute COVID‐19 syndrome (PCS) and conducted meta‐regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post‐COVID‐19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random‐effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ‐VAS) was (59%; 95% CI: 42%–75%). Based on individual factors in the EQ‐5D‐5L questionnaire, the prevalence of mobility was (36, 10–67), personal care (8, 1–21), usual quality (28, 2–65), pain/discomfort (42, 28–55), and anxiety/depression (38, 19–58). The prevalence of persistent symptoms was fatigue (64, 54–73), dyspnea (39.5, 20–60), anosmia (20, 15–24), arthralgia (24.3, 14–36), headache (21, 3–47), sleep disturbances (47, 7–89), and mental health (14.5, 4–29). Meta‐regression analysis showed the poor quality of life was significantly higher among post‐COVID‐19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.

The COVID-19 virus was first reported in Wuhan China in December 2019. Since its inception, the virus has spread globally and resulted in a pandemic. As of March 2021, the virus has infected 125 million people and has resulted in 2.7 million deaths worldwide. 1 Over the last year, there has been remarkable scientific progress in uncovering the disease mechanism and creating vaccines against the virus. Although there now seems to be light at the end of a long tunnel, the virus still continues to infect people. Although the symptoms of COVID-19 in the majority of cases are limited to fever, fatigue, cough, diarrhea, anosmia, and headache, in some cases it can cause more severe complications including end-organ damage. 2, 3 Manifestations of end-organ damage can include but are not limited to acute respiratory distress syndrome (ARDS), cardiac injuries (ventricular arrhythmias and hemodynamic instability), thrombotic manifestations, renal, hepatic, and gastrointestinal damage. [4] [5] [6] There is well-known literature on the acute manifestations of the COVID-19 as well as the complications, but long-term COVID-19 effects after recovery or discharge from the hospital have not been established well.

According to the CDC/IDSA, post-acute COVID-19 syndrome (PCS) is defined as an ongoing symptomatic illness in patients who have recovered from their initial COVID-19 infection. 7, 8 The type of persistent symptoms, their prevalence, duration, and severity following recovery of COVID-19, as well as risk factors causing them, are still under investigation. A few studies have reported a wide array of persistent symptoms after COVID-19 hospitalizations as well as outpatient recovery. These persistent symptoms include fatigue, dyspnea, anosmia, sleeping difficulties, chest pain, headache, cough, and mental health problems. 6, [9] [10] [11] [12] [13] [14] [15] The mechanisms behind these symptoms are not very well understood. One study suggested that they may be associated with active long-term biochemical and inflammatory response pathways. 16 Another explanation is that these manifestations may arise because of hypoxia and hypoxemia secondary to the destruction of capillaries. 17 However, more studies are required to determine the exact cause of these persistent symptoms. These long-term symptoms may have a significant effect on the quality of life and cause posttraumatic stress disorder (PTSD). 9, 11 Persistent symptoms after post-viral infection is not a novel concept as there is evidence of similar effects seen in SARS [18] [19] [20] Studies have shown that patients infected with SARS often experienced long-term fatigue, myalgia encephalomyelitis, anorexia, and hypocortisolism. 18 15 another study has reported a significant drop in EQ. 5D in ICU (68%) versus ward (45%) patients. 14 More evidence is required on this before we can make any definitive conclusions.

In this meta-analysis, we aim to evaluate the pooled prevalence of poor quality of life in patients post-COVID-19. We also aim to perform meta-regression to evaluate the effects of persistent symptoms and ICU admission on the poor quality of life. questionnaire.

Poor quality of life is assessed using: 1) VAS scale (0-100): The EQ-VAS is a patient's subjective assessment of generic health ranging from 0 to 100, with higher scores representing better subjective health experience.

2) The EQ-5D-5L is a validated questionnaire to evaluate a patient's quality of life by assessing the following five factors: mobility, selfcare, usual activities, pain or discomfort, and anxiety or depression.

Categorization within each factor is divided into five levels that range from no problems to extreme problems 22 and https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/.

We also aim to evaluate the pooled prevalence of persistent symptoms in PCS and perform a meta-regression to evaluate the effects of persistent symptoms and ICU admission on the poor quality of life.

A systematic review was performed using the PRISMA protocol. 23 We searched PubMed for observational studies that 

Abstracts and full-length articles were reviewed for the availability of data on the poor quality of life in COVID-19 patients after recovery for quantitative analysis. PM and UP independently screened all of the identified studies and assessed full texts to determine eligibility. Any disagreement was resolved through consensus.

Data were extracted by two authors (P. M. and U. P.). The descriptive variables extracted were the author's name, country, study type, follow-up time, the severity of COVID-19, sample size, mean age and percentage of males, persistent symptoms, and instrument used to measure QoL are presented in Table 1 .

We used the MetaXL software to estimate the pooled prevalence, patients. Comprehensive Meta-Analysis software (Biostat Inc.) was used to estimate correlation coefficient (r), 95% CI, odds ratios [e^coefficient], p-value, and I 2 using a random-effects model due to expected heterogeneity. I 2 values of 25%, 50%, and 75% represented low, medium, and high heterogeneity. p < 0.05 was considered significant.

Initially, 1725 publications were screened. Out of which 50 full-text articles were assessed for eligibility using inclusion and exclusion criteria. 28 studies were excluded because they had no information on the poor quality of life and persistent symptoms. After a detailed assessment, as of Figure 2 ).

Four studies have reported mean EQ-VAS. The pooled mean EQ-VAS of poor quality of life was 81.1, 95% CI: 75.6-86.5) (Table 3 and Figure 3 ).

The pooled prevalence of individual factors in EQ-5D-5L questionnaire estimating poor quality of life was mobility (36%, 95% CI:

10%-67%), personal care (8%, 95% CI: 1%-21%), usual quality (28%, 95% CI: 2%-65%), pain/discomfort (42%, 95% CI: 28%-55%), anxiety/depression (38%, 95% CI: 19%-58%) ( Table 2 and Figure 4A -E).

There was a total of nine most commonly reported persistent symptoms identified in post-COVID-19 patients in the literature reviewed. The prevalence of all the persistent symptoms is presented in (Figure 5A,B) . There was no significant correlation between dyspnea, anosmia, and poor quality of life survivors. 9, 32 There is evidence of PTSD in post-COVID-19 but the risk factors causing it is not clearly described and need further evidence. 32 24 Moreover, in many patients, the persistent symptoms force them to have reduced hours at work or quit altogether which may increase their financial distress. 24 In addition, many tivity. This cough sensitivity can be enhanced for months after a viral infection. 35 Finally, there have been multiple mechanisms proposed for COVID-related anosmia. One study showed that a specialized group of cells in the olfactory epithelium express high levels of ACE 2 receptor, which is used by coronavirus to invade the cells and cause infection. As the support network for olfactory cells is affected, olfactory cells may not properly develop resulting in loss of smell. 36 Another mechanism that could potentially explain anosmia has its basis in inflammatory products. As the olfactory bulb is immunogenic, inflammatory products released as a result of COVID-19 may lead to selective damage of cells resulting in anosmia. 37 Although there is still debate over the exact mechanisms behind these long-term symptoms, one thing remains clear; the presence of these symptoms has significant psychological impacts including mental health implications, increased stress, and decreased HRQoL 10, 11, 14 As and also the treatment guidelines of PCS patients. There are few hypotheses supporting these findings but there is no definitive answer to why certain patients develop PCS and its overall mechanism of action. Understanding the risk factors and pathophysiology will allow us to better manage these PCS patients.

In our meta-analysis, we found that PCS has been associated with poor quality of life, long-term persistent symptoms including fatigue, dyspnea, anosmia, cough, sleep disturbances, chest pain, arthralgia, and worse overall mental health. Although there is established literature on persistent symptoms associated with PCS, risk factors for developing it still remain unclear. These gaps in our understanding can partially be attributed to the fact that the primary focus to combat the pandemic, was developing vaccines. However, due to the large COVID-19 infected population which has recovered and some of whom have developed PCS, the healthcare focus should shift in understanding the risk factors causing PCS eventually leading to poor quality of life, and developing follow-up and treatment strategies accordingly.

The authors declare that there are no conflict of interests. Shreejith Pillai and Urvish Patel.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

http://orcid.org/0000-0002-9427-0225

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