Emerging evidence has shown that COVID-19 survivors could suffer from persistent symptoms. However, it remains unclear whether these symptoms persist over the longer term. This study aimed to systematically synthesise evidence on post-COVID symptoms persisting for at least 12 months. We searched PubMed and Embase for papers reporting at least one-year follow-up results of COVID-19 survivors published by 6 November 2021. Random-effects meta-analyses were conducted to estimate pooled prevalence of specific post-COVID symptoms. Eighteen papers that reported one-year follow-up data from 8591 COVID-19 survivors were included. Fatigue/weakness (28%, 95% CI: 18–39), dyspnoea (18%, 95% CI: 13–24), arthromyalgia (26%, 95% CI: 8–44), depression (23%, 95% CI: 12–34), anxiety (22%, 95% CI: 15–29), memory loss (19%, 95% CI: 7–31), concentration difficulties (18%, 95% CI: 2–35), and insomnia (12%, 95% CI: 7–17) were the most prevalent symptoms at one-year follow-up. Existing evidence suggested that female patients and those with more severe initial illness were more likely to suffer from the sequelae after one year. This study demonstrated that a sizeable proportion of COVID-19 survivors still experience residual symptoms involving various body systems one year later. There is an urgent need for elucidating the pathophysiologic mechanisms and developing and testing targeted interventions for long-COVID patients.

/pdf/long-term-sequelae-of-covid-19-a-systematic-review-and-meta-1lp10sjx.pdf

Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms

Coronavirus disease 2019 (COVID‐19) often causes radiological and functional pulmonary sequelae. However, evidence on 1‐year follow‐up of pulmonary sequelae is limited. We aimed to investigate the characteristics and time‐course of pulmonary sequelae after recovery from COVID‐19 through 1‐year follow‐up. We searched PubMed and EMBASE databases on 25 February 2022, and included studies with computed tomography (CT) findings at the 1‐year follow‐up. The extracted data on CT findings were analysed using a one‐group meta‐analysis. We further analysed the data in relation to COVID‐19 severity, improvement rate and lung function. Fifteen eligible studies (N = 3134) were included. One year after COVID‐19, 32.6% (95% CI 24.0–42.6, I2 = 92.9%) presented with residual CT abnormalities. Ground‐glass opacity and fibrotic‐like changes were frequently observed in 21.2% (95% CI 15.4–28.4, I2 = 86.7%) and 20.6% (95% CI 11.0–35.2, I2 = 91.9%), respectively. While the gradual recovery was seen on CT (52.9% [mid‐term] vs. 32.6% [1 year]), the frequency of CT abnormalities was higher in the severe/critical cases than in the mild/moderate cases (37.7% vs. 20.7%). In particular, fibrotic changes showed little improvement between 4–7 months and 1 year after COVID‐19. Pulmonary function tests at 1 year also showed the decline in diffusing capacity of the lung for carbon monoxide, especially in severe/critical cases. Our meta‐analysis indicated that residual CT abnormalities were common in hospitalized COVID‐19 patients 1 year after recovery, especially fibrotic changes in severe/critical cases. As these sequelae may last long, vigilant observations and longer follow‐up periods are warranted.

One‐year follow‐up CT findings in COVID‐19 patients: A systematic review and meta‐analysis

We aimed to review the data available to evaluate the long-term consequences of coronavirus disease 2019 (COVID-19) at 6 months and above. We searched relevant observational cohort studies up to 9 February 2022 in Pubmed, Embase, and Web of Science. Random-effects inverse-variance models were used to evaluate the Pooled Prevalence (PP) and its 95% confidence interval (CI) of long-term consequences. The Newcastle–Ottawa quality assessment scale was used to assess the quality of the included cohort studies. A total of 40 studies involving 10,945 cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were included. Of the patients, 63.87% had at least one consequence at the 6 month follow-up, which decreased to 58.89% at 12 months. The most common symptoms were fatigue or muscle weakness (PP 6–12 m = 54.21%, PP ≥ 12 m = 34.22%) and mild dyspnea (Modified Medical Research Council Dyspnea Scale, mMRC = 0, PP 6–12 m = 74.60%, PP ≥ 12 m = 80.64%). Abnormal computerized tomography (CT; PP 6–12 m = 55.68%, PP ≥ 12 m = 43.76%) and lung diffuse function impairment, i.e., a carbon monoxide diffusing capacity (DLCO) of < 80% were common (PP 6–12 m = 49.10%, PP ≥ 12 m = 31.80%). Anxiety and depression (PP 6–12 m = 33.49%, PP ≥ 12 m = 35.40%) and pain or discomfort (PP 6–12 m = 33.26%, PP ≥ 12 m = 35.31%) were the most common problems that affected patients’ quality of life. Our findings suggest a significant long-term impact on health and quality of life due to COVID-19, and as waves of ASRS-CoV-2 infections emerge, the long-term effects of COVID-19 will not only increase the difficulty of care for COVID-19 survivors and the setting of public health policy but also might lead to another public health crisis following the current pandemic, which would also increase the global long-term burden of disease.

/pdf/long-term-consequences-of-covid-19-at-6-months-and-above-a-20erq7v0.pdf

Long-Term Consequences of COVID-19 at 6 Months and Above: A Systematic Review and Meta-Analysis

Background: Long Covid occurs in those infected with SARSCoV2 whose symptoms persist or develop beyond the acute phase. We conducted a systematic review to determine the prevalence of persistent symptoms, functional disability or pathological changes in adults or children at least 12 weeks post-infection. Methods: We searched MEDLINE (Ovid), Embase (OVID), the Cochrane Covid-19 Study register, WHO ICTRP, medRxiv, Cochrane CENTRAL, MEDLINE (PubMed), ClinicalTrials.gov, and the WHO Global research on coronavirus disease (COVID-19) database from 1st January 2020 to 2nd November 2021, limited to publications in English. We included studies with at least 100 participants. Studies where all participants were critically ill were excluded. Articles were screened independently by two reviewers, with disagreements resolved by a third. Long Covid (primary outcome) was extracted as prevalence of at least one symptom or pathology, or prevalence of the most common symptom or pathology, at 12 weeks or later. Heterogeneity was quantified in absolute terms and as a proportion of total variation and explored across pre-defined subgroups (PROSPERO ID CRD42020218351). Findings: In total 120 studies in 130 publications were included. Length of follow-up varied from 12 weeks to over 12 months. Few studies had low risk of bias. All complete and subgroup analyses except one had I2 [≥] 90%, with prevalence of persistent symptoms ranging between 0% and 93%. Studies using routine healthcare records tended to report lower prevalence of persistent symptoms/pathology than self-report. However, studies systematically investigating pathology in all participants at follow up tended to report the highest estimates of all three. Studies of hospitalised cases had generally higher estimates than community-based studies. Interpretation: The way in which Long Covid is defined and measured affects prevalence estimation. Given the widespread nature of SARSCoV2 infection globally, the burden of chronic illness is likely to be substantial even using the most conservative estimates.

/pdf/systematic-review-of-the-prevalence-of-long-covid-hitg1fvm.pdf

Systematic Review of the Prevalence of Long COVID

Abstract Infection with SARS-CoV-2 causes wide range of disease severities from asymptomatic to life-threatening disease. Understanding the contribution of immunological traits in immunity against SARS-CoV-2 and in protection against severe COVID-19 could result in effective measures to prevent development of severe disease. While the role of cytokines and antibodies has been thoroughly studied, this is not the case for T cells. In this review, the association between T cells and COVID-19 disease severity and protection upon reexposure is discussed. While infiltration of overactivated cytotoxic T cells might be harmful in the infected tissue, fast responding T cells are important in the protection against severe COVID-19. This protection could even be viable in the long term as long-living memory T cells seem to be stabilized and mutations do not appear to have a large impact on T cell responses. Thus, after vaccination and infections, memory T cells should be able to help prevent onset of severe disease for most cases. Considering this, it would be useful to add N or M proteins in vaccinations, alongside the S protein which is currently used, as this results in a broader T cell response. 

/pdf/role-of-t-cells-in-severe-covid-19-disease-protection-and-12uzhqtg.pdf

Role of T cells in severe COVID-19 disease, protection, and long term immunity

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.

/pdf/sars-cov-2-immunity-and-functional-recovery-of-covid-19-4wo74392je.pdf

SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection.

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SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection.