A systematic review and meta‐analysis of long‐term sequelae of COVID‐19 2‐year after SARS‐CoV‐2 infection: A call to action for neurological, physical, and psychological sciences

Abstract

Long‐term sequelae conditions of COVID‐19 at least 2‐year following SARS‐CoV‐2 infection are unclear and little is known about their prevalence, longitudinal trajectory, and potential risk factors. Therefore, we conducted a comprehensive meta‐analysis of survivors' health‐related consequences and sequelae at 2‐year following SARS‐CoV‐2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to February 10, 2023. A systematic review and meta‐analysis were performed to calculate the pooled effect size, expressed as event rate (ER) with corresponding 95% confidence interval (CI) of each outcome. Twelve studies involving 1 289 044 participants from 11 countries were included. A total of 41.7% of COVID‐19 survivors experienced at least one unresolved symptom and 14.1% were unable to return to work at 2‐year after SARS‐CoV‐2 infection. The most frequent symptoms and investigated findings at 2‐year after SARS‐CoV‐2 infection were fatigue (27.4%; 95% CI 17%–40.9%), sleep difficulties (25.1%; 95% CI 22.4%–27.9%), impaired diffusion capacity for carbon monoxide (24.6%; 95% CI 10.8%–46.9%), hair loss (10.2%; 95% CI 7.3%–14.2%), and dyspnea (10.1%; 95% CI 4.3%–21.9%). Individuals with severe infection suffered more from anxiety (OR = 1.69, 95% CI 1.17–2.44) and had more impairments in forced vital capacity (OR = 9.70, 95% CI 1.94–48.41), total lung capacity (OR = 3.51, 95% CI 1.77–6.99), and residual volume (OR = 3.35, 95% CI 1.85–6.07) after recovery. Existing evidence suggest that participants with a higher risk of long‐term sequelae were older, mostly female, had pre‐existing medical comorbidities, with more severe status, underwent corticosteroid therapy, and higher inflammation at acute infection. Our findings suggest that 2‐year after recovery from SARS‐CoV‐2 infection, 41.7% of survivors still suffer from either neurological, physical, and psychological sequela. These findings indicate that there is an urgent need to preclude persistent or emerging long‐term sequelae and provide intervention strategies to reduce the risk of long COVID.

Lactate dehydrogenase contribution to symptom persistence in long COVID: A pooled analysis

“…Emerging evidence from a pooled analysis of 1, 289, 044 study participants from 12 studies reports a 24.6% prevalence for impaired lung diffusion capacity among COVID-19 survivors up to 2 years after recovery from SARS-CoV-2 infection. 3 Similar evidence from a pooled analysis of 28 studies up to 6 months after recovery from SARS and MERS revealed impaired lung diffusion capacity at a prevalence of 27%. 74 However, a recent study by Peixun Zhang and colleagues followed up 71 healthcare workers for up to 15 years after recovery from SARS infection and reported that most recovery from pulmonary impairment occurred in the first 2 years (first year in 2003 = 9%; second year in 2004 = 3.2%) but persisted thereafter up to 15 years (15 th year in 2018 = 4.6%).…”

“…1 According to the Centre for Disease Control, long COVID is defined as a post-COVID-19 condition in which there is new, evolving or persistent health issues occurring ≥4 weeks after SARS-CoV-2 infection 2 Emerging evidence reports that fatigue (27.4%), anosmia (25%), impaired lung diffusion capacity (24.6%), alopecia (10.2%), and dyspnoea (10.1%) are the most frequent symptoms and findings in COVID-19 survivors 2 years after SARS-CoV-2 infection. 3 Lactate dehydrogenase (LDH) is a predominantly cytoplasmic (oxidoreductase) enzyme of cytosol of glycolytic cells and tissues; specifically, LDH catalyses the conversion of pyruvate to lactate using NADH (reduced nicotinamide adenine dinucleotide). 4 LDH also appears in the mitochondrial reticulum where it catalyses the oxidation of lactate to pyruvate for entry into the TCA Cycle.…”

“…1 Globally, labour force has struggled owing to a good number of long COVID patients that are yet to return to their original work and presently, there are no known effective pharmacological or non-pharmacological interventions. 1,3,9 Though myriads of pathophysiological factors have been implicated including dysregulated immune response that results in some degree of tissue damage, 10 the exact cause of residual symptoms remains unclear. 11 Previous studies had shown that raised plasma LDH is associated with the risk of having severe.…”

Post-COVID-19 neuropsychiatric manifestations: a suggested therapeutic approach to ‘long COVID’ with azithromycin

“…Clearly, it has the potential neurological and psychiatric features long established with RNA viruses such as influenza virus and, more recently, with coronaviruses [14,15]. Since scientific evidence is weak at this time [16][17][18][19][20], we strongly encourage clinical trials on long COVID with azithromycin to confirm or refute the value of this potentially efficient, cost-effective, readily available, easy-to-use, and relatively safe medication.…”

Neutrophil degranulation, endothelial and metabolic dysfunction in unvaccinated long COVID patients

“…In another large Chinese cohort, 49% of COVID‐19 survivors had persistent symptoms after 12 months 2 . A meta‐analysis revealed that about 80% of patients who experienced an acute SARS‐CoV‐2 infection can develop one or more symptoms in the long‐term, 3 and up to 14.1% of them are still unable to return to work 2 years following the acute infection 4 . The most frequent clinical manifestations of long COVID are fatigue, dyspnea, chest discomfort, cough, anosmia, sleep difficulties, hair loss 4–12 .…”