Long COVID is a novel emerging syndrome known to affect multiple health areas in patients previously infected by SARS-CoV-2 markedly impairing their quality of life. The pathophysiology of Long COVID is still largely poorly understood and multiple mechanisms were proposed to underlie its occurrence, including alterations in the hormonal hypothalamic-pituitary axes. Aim of this review is to present and discuss the potential negative implications of these hormonal dysfunctions in promoting and influencing the Long COVID syndrome. To date, the hypothalamic-pituitary-adrenal axis is the mostly investigated and several studies have reported a prolonged impairment leading to mild and subclinical forms of central adrenal insufficiency. Few data are also available regarding central hypogonadism, central hypothyroidism and growth hormone (GH) deficiency. A high prevalence of central hypogonadism in COVID-19 survivors several months after recovery was consistently reported in different cohorts. Conversely, very few data are available on the hypothalamic-pituitary-thyroid axis function that was mainly shown to be preserved in COVID-19 survivors. Finally, a potential impairment of the hypothalamic-GH axis in Long COVID has also been reported. These data altogether may suggest a novel possible pituitary-centred pathophysiological view of Long COVID syndrome which if confirmed by large clinical studies may have relevant implication for the diagnostic and therapeutic approach at least in a subset of patients with the syndrome.

The novel coronavirus strain SARS-CoV-2 triggered the COVID-19 pandemic with severe economic and social ramifications. As the pathophysiology of SARS-CoV-2 infection in the respiratory system becomes more understood, growing evidence suggests that the virus also impacts the homeostasis-regulating neuroendocrine system, potentially affecting other organ systems.

This review explores the interactions between SARS-CoV-2 and the neuroendocrine system, highlighting the effect of this virus on various endocrine glands, including the brain, hypothalamus, pituitary, pineal, thyroid, parathyroid, adrenal glands, pancreatic islets, gonads, and adipose tissue. The viral invasion disrupts normal hormonal pathways, leading to a range of endocrine disorders, immune dysregulation, and metabolic disturbances.

There is potential for SARS-CoV-2 to induce autoimmune responses, exacerbate existing endocrine conditions, and trigger new-onset disorders. Understanding these interactions is crucial for developing treatment strategies that address not only the respiratory symptoms of COVID-19 but also its endocrine complications. The review emphasizes the need for further research to elucidate the long-term effects of SARS-CoV-2 on endocrine health.

Previous studies suggest that patients' thyroid status might directly impact the course of Coronavirus disease 2019 (COVID-19). The objective of the study was to determine the clinical profile of COVID-19 patients with hypothyroidism and compare it with that of COVID-19 patients without hypothyroidism.

Retrospective observational study.

The study was conducted in a tertiary healthcare centre in Tamil Nadu between May and June 2021.

The study included 117 patients admitted with hypothyroidism and COVID-19 as well as 117 age and Gender matched COVID-19 patients without hypothyroidism.

Data regarding the demography, comorbidities, presenting symptoms, method of diagnosis of COVID-19, computed tomography (CT) severity score, Interleukin 6 (IL-6), D-dimer, oxygen requirement, number of days in hospital and outcome were collected for both groups. Data analysis was conducted, and p<0.05 was considered statistically significant.

The study comprised 234 patients over two months, from May to June 2021. Distribution of presenting symptoms showed that the hypothyroidism group presented with a higher incidence of fever (66.67%), loose stool (18.80%) and myalgia (7.69%). Results show that RTPCR+, O2 Requirement, death, D-dimer, IL-6, number of days admitted as well as CT-severity did not show any statistically significant differences (p>0.05) between both groups. The outcomes also showed that both groups reported four mortalities.

The results of the study help conclude that the hypothyroidism status of a COVID-19 patient is not associated with higher severity of clinical symptoms, deranged laboratory values as well as mortality.

None declared.

Multiple factors have engaged in the progression of thyroid cancer (TC). Recent studies have shown that viral infection can be a critical factor in the pathogenesis of TC. Viruses, such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may play an essential role in the occurrence, development, and even prognosis in TC. This review mainly explored the potential role of viral infection in the progress of TC. The possible mechanisms could be recognizing the host cell, binding to the receptors, affecting oncogenes levels, releasing viral products to shape a beneficial environment, interacting with immune cells to induce immune evasion, and altering the pituitary-thyroid axis. Thus, comprehensive knowledge may provide insights into finding molecular targets for diagnosing and treating virus-related TC.

Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights.

In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s).

Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n = 10 studies; n = 989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n = 19 studies; n = 2606 participants), or neutralizing response (n = 7 studies; n = 1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders.

Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.

Monoclonal antibodies (mAbs) have shown clinical benefits against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have reported the use of bamlanivimab as a promising treatment option for COVID-19.

To synthesize the latest evidence for the efficacy and safety of bamlanivimab alone in the treatment of adult patients with COVID-19.

A literature search was conducted in PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar using "SARS-CoV-2", "COVID-19", "LY-CoV555", and "Bamlanivimab" keywords up to January 25, 2023. The quality of included studies was assessed using the Cochrane bias tools. The Comprehensive Meta-Analysis software version 3.0 was used to analyze the data.

A total of 30 studies involving 47368 patients were included. A significant difference was observed between the bamlanivimab and standard of care/placebo groups in terms of mortality rate [risk ratio (RR) = 50, 95% confidence interval (CI): 0.36-0.70], hospitalization rate (RR = 0.51; 95%CI: 0.39-0.68), and emergency department (ED) visits (RR = 0.69; 95%CI: 0.47-0.99); while the two groups exhibited no significant difference in terms of intensive care unit (ICU) admission (P > 0.05). Compared to other mAbs, bamlanivimab was associated with a higher rate of hospitalization (RR = 1.44; 95%CI: 1.07-1.94). However, no significant difference was detected between the bamlanivimab and other mAbs groups in terms of mortality rate, ICU admission, and ED (P > 0.05). The incidence of any adverse events was similar between the bamlanivimab and control groups (P > 0.05).

Although the results suggest the efficacy and safety of bamlanivimab in COVID-19 patients, further research is required to confirm the efficacy of this drug for the current circulating SARS-CoV-2 variants.

Post-COVID-19 syndrome (PCS-19) is a condition characterized by both physical and cognitive alterations in patients who have overcome COVID-19. Despite the high incidence of this disorder and the inconveniences it produces to those affected, there are few studies investigating the efficacy of cognitive stimulation in these patients. The aim of this study was to compare two groups of patients with PCS-19. One of them was treated with neuropsychological intervention for 6 months, whereas the other did not receive treatment. Both groups shared similar clinical characteristics and cognitive profiles.

The study included 15 participants. Eight (seven women and one man, with a mean age of 50.13 years) made up the experimental group and received neuropsychological rehabilitation sessions once a week with the aim of recovering or compensating for their impaired functions. The control group consisted of seven patients (six women and one man, with a mean age of 52.86 years) who did not undergo neuropsychological rehabilitation sessions. The neuropsychological assessment protocol included tests for all cognitive domains.

In comparison with the assessment prior to the neuropsychological intervention, significant differences were found in the experimental group both in verbal memory and in the action naming task. As for the control group, improvements in action fluency performance were observed. Neither group showed significant improvement in pre- versus posttest Stroop scores. However, the control group did perform higher than the treatment group in the final assessment.

Despite the small sample size, our results suggest that patients with PCS-19 may benefit from neuropsychological rehabilitation, as it may help them to improve several cognitive functions that do not recover spontaneously.

The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to a lack of recognition of the condition and knowledge of the underlying mechanisms. In fact, the prevalence of post-COVID symptoms ranges from 50% during the first months after the infection up to 20% two-years after. This perspective review aimed to map the existing literature on post-COVID symptoms and to identify gaps in the literature to guide the global effort toward an improved understanding of long-COVID and suggest future research directions. There is a plethora of symptomatology that can be due to COVID-19; however, today, there is no clear classification and definition of this condition, termed long-COVID or post-COVID-19 condition. The heterogeneity in the symptomatology has led to the presence of groups/clusters of patients, which could exhibit different risk factors and different mechanisms. Viral persistence, long-lasting inflammation, immune dysregulation, autoimmune reactions, reactivation of latent infections, endothelial dysfunction and alteration in gut microbiota have been proposed as potential mechanisms explaining the complexity of long-COVID. In such an equation, viral biology (e.g., re-infections, SARS-CoV-2 variants), host biology (e.g., genetics, epigenetics) and external factors (e.g., vaccination) should be also considered. These various factors will be discussed in the current perspective review and future directions suggested.

SARS-CoV-2 virus responsible for acute respiratory disease affected other organs leading to co-existence symptoms or complications. Thyroid gland was one of them due to expression of angiotensin-converting enzyme 2 (ACE2), the protein facilitating viral binding to the host cells. Moreover, thyroid gland, important for regulation of hormonal network, is extremely sensitive to any changes in homeostasis and metabolism. It was shown, that COVID-19 was associated with induction of thyroid disease or increasing existing functional disturbances or autoimmune process. Thyroid diseases are mainly based on immunological pathomechanism although the relation between immune system and thyroid function is bidirectional e.g. thyroid hormones modulate specific immune responses, including cell-mediated immunity, NK cell activity, the production of antiviral interferon (IFN) and proliferation of T- and B-lymphocytes. The effects of COVID-19 and mRNA vaccine on thyroid function and diseases are discussed.

The correlation between acute coronavirus disease 2019 (COVID-19) and subacute thyroiditis (SAT) has not been clearly investigated in "long COVID" patients. We aimed to investigate the incidence of SAT during convalescence and after the acute phase of COVID-19, comparing with that of the general population.

Data from a total of 422,779 COVID-19 patients and a control group of 2,113,895 individuals were analyzed. The index date was defined as the date 3 months after confirmation of COVID-19. The incidence rate (IR) of SAT and hazard ratios (HRs) were calculated per 100,000 persons. Subgroup analysis included analysis of HRs 90-179 and 180 days post-COVID-19 diagnosis; and additional analysis was conducted according to hospitalization status, sex, and age group.

The IR of SAT was 17.28 per 100,000 persons (95% confidence interval [CI], 12.56 to 23.20) in the COVID-19 group and 8.63 (95% CI, 6.37 to 11.45) in the control group. The HR of COVID-19 patients was 1.76 (95% CI, 1.01 to 3.06; P=0.045). The HR of SAT was 1.39 (95% CI, 0.82 to 2.34; P=0.220) up to 6 months after the index date and 2.30 (95% CI, 1.60 to 3.30; P<0.001) beyond 6 months. The HR for SAT among COVID-19 patients was 2.00 (95% CI, 1.41 to 2.83) in hospitalized patients and 1.76 (95% CI, 1.01 to 3.06) in non-hospitalized patients compared to the control group. The IR of SAT was 27.09 (95% CI, 20.04 to 35.82) for females and 6.47 (95% CI, 3.34 to 11.30) for males. In the 19 to 64 age group, the IR of SAT was 18.19 (95% CI, 13.70 to 23.67), while the IR was 9.18 (95% CI, 7.72 to 10.84) in the 65 to 69 age group.

SAT could be a potential long-term complication of COVID-19. Long-term surveillance for thyroid dysfunction is needed especially in hospitalized, female and young-aged subjects.

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease outbreak initiated in 2019 (COVID-19) has been shown to affect the health of infected patients in a manner at times dependent on pre-existing comorbidities. Reported here is an overview of the correlation between comorbidities and the exacerbation of the disease in patients with COVID-19, which may lead to poor clinical outcomes or mortality. General medical issues are also reviewed, such as the types of symptoms present in people infected with SARS-CoV-2, the long-term effects of COVID-19 disease, and the types of treatment that are currently used.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system but can also lead to neurological complications. Among COVID-19 patients, the endothelium is considered the Achilles heel. A variety of endothelial dysfunctions may result from SARS-CoV-2 infection and subsequent endotheliitis, such as altered vascular tone, oxidative stress, and cytokine storms. The cerebral hemodynamic impairment that is caused is associated with a higher probability of severe disease and poor outcomes in patients with COVID-19. This review summarizes the most relevant literature on the role of vasomotor reactivity (VMR) in COVID-19 patients. An overview of the research articles is presented. Most of the studies have supported the hypothesis that endothelial dysfunction and cerebral VMR impairment occur in COVID-19 patients. Researchers believe these alterations may be due to direct viral invasion of the brain or indirect effects, such as inflammation and cytokines. Recently, researchers have concluded that viruses such as the Human Herpes Virus 8 and the Hantavirus predominantly affect endothelial cells and, therefore, affect cerebral hemodynamics. Especially in COVID-19 patients, impaired VMR is associated with a higher risk of severe disease and poor outcomes. Using VMR, one can gain valuable insight into a patient's disease progression and make more informed decisions regarding appropriate treatment options. A new pandemic may develop with the COVID-19 virus or other viruses, making it essential that healthcare providers and researchers remain focused on developing new strategies for improving survival in such patients, particularly those with cerebrovascular risk factors.

The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19.

In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated.

Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients' backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/L, interquartile range (IQR): 58.8-353.8) than in the non-ME/CFS group (98.2 μg/L, 40.4-251.5) and no-fatigue group (86.7 μg/L, 37.5-209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05).

Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients.

As the SARS-CoV-2-induced pandemic wanes, a substantial number of patients with acute Corona Virus-induced disease (COVID-19 continue to have symptoms for a prolonged time after initial infection. These patients are said to have postacute sequelae of COVID (PASC) or "long COVID". The underlying pathophysiology of this syndrome is poorly understood and likely quite heterogeneous. The role of persistent, possibly deviant inflammation as a major factor in comorbidity is suspected.

To review data that address the relative importance of inflammation in the pathophysiology spectrum of PASC and to address how this would impact diagnosis and approach to therapy in patients identified as having such inflammatory abnormalities.

A review of public databases, including PubMed, MeSH, NLM catalog, and clinical trial databases such as clinicaltrials.gov.

The literature supports a prominent role for various forms and types of inflammation in the pathophysiologic spectrum of PASC. Such inflammation can be persistent ant CoV-2-specific responses, new onset autoimmune responses, or a loss of normal immunoregulation resulting in widespread, sustained inflammatory pathologies that can affect both broad constitutional symptoms (such as fatigue, neurocognitive dysfunction, and anxiety/depression) and organ-specific dysfunction and/or failure.

PASC is a significant clinical entity with similarities to and differences from other postviral syndromes. Significant research efforts are ongoing to better understand specific aberrant inflammatory pathways present in individual patients for the purpose of developing and implementing effective therapies and ultimately prophylaxis strategies to prevent the progression of COVID-19 as well as likely future viral illnesses and pandemics.

Severe respiratory failure is one of the most serious complications of coronavirus disease 2019 (COVID-19). In a small proportion of patients, mechanical ventilation fails to provide adequate oxygenation and extracorporeal membrane oxygenation (ECMO) is needed. The surviving individuals need long-term follow-up as it is not clear what their prognosis is.

To provide a complex clinical picture of patients during follow-up exceeding one year after the ECMO therapy due to severe COVID-19.

All subjects involved in the study required ECMO in the acute stage of COVID-19. The survivors were followed-up for over one year at a specialized respiratory medical center.

Of the 41 patients indicated for ECMO, 17 patients (64.7% males) survived. The average age of survivors was 47.8 years, and the average BMI was 34.7 kg·m^-2. The duration of ECMO support was 9.4 days. A mild decrease in vital capacity (VC) and transfer factor (DLCO) was observed on the initial follow-up visit (82.1% and 60%, respectively). VC improved by 6.2% and by an additional 7.5% after 6 months and 1 year, respectively. DLCO improved by 21.1% after 6 months and remained stable after 1 year. Post-intensive care consequences included psychological problems and neurological impairment in 29% of patients; 64.7% of the survivors got vaccinated against SARS-CoV-2 within 12 months of hospitalization and 17.6% experienced reinfection with a mild course.

The COVID-19 pandemic has significantly increased the need for ECMO. Patients' quality of life after ECMO is temporarily significantly reduced but most patients do not experience permanent disability.

Coronavirus disease 2019 (COVID-19) has spread and become a substantial public health concern worldwide [...].

A substantial proportion of people with acute COVID-19 develop post-COVID-19 condition (previously known as long-COVID) characterized by symptoms that persist for months after the initial infection, including neuropsychological sequelae. Post-COVID-19 condition frequency varies greatly according to different studies, with values ranging from 4 to 80% of the COVID-19 patients. Yoga is a psycho-somatic approach that increases physical, mental, emotional and spiritual strength, and connection. Yoga practice enhances innate immunity and mental health, so it can be used as complementary therapy in the COVID-19 treatment, namely the post-COVID-19 condition. In this article, we conducted a literature review on yoga and COVID-19, finding that an intervention comprising asana, pranayama, and meditation may be a strategy of choice for these patients' recovery. However, further studies are needed to show its effectiveness in this, still unknown, context.

This work identifies new ligands of the nucleoprotein N of SARS-CoV-2 by in silico screening, which used a new model of N, built from an Alphafold model refined by molecular dynamic simulations. The ligands were neuropeptides, such as substance P (1-7) and enkephalin, bound at a large site of the C-terminal or associated with the N-terminal β-sheet. The BA4 and BA5 Omicron variants of N also exhibited a large site as in wt N, and an increased flexibility of the BA5 variant, enabling substance P binding. The binding sites of some ligands deduced from modeling in wt N were assessed by mutation studies in surface plasmon resonance experiments. Dynamic light scattering showed that the ligands impeded RNA binding to N, which likely inhibited replication. We suggest that the physiological role of these neuropeptides in neurotransmission, pain and vasodilation for cholecystokinin and substance P could be altered by binding to N. We speculate that N may link between viral replication and multiple pathways leading to long COVID-19 symptoms. Therefore, N may constitute a "danger hub" that needs to be inhibited, even at high cost for the host. Antivirals targeted to N may therefore reduce the risk of brain fog and stroke, and improve patients' health.

A significant number of individuals experience post-COVID-19 symptoms, but knowledge of perceived consequences and life satisfaction is lacking. Here, we investigate perceived consequences regarding everyday life, health, physical activity and work post-COVID-19 and factors associated with low life satisfaction. A total of 766 people (mean age 48; 672 women) experiencing post-COVID-19 symptoms at least two months after infection (mean 13 months) responded to an online survey. A majority (≥77%) perceived physical fatigue, mental fatigue, dizziness, reduced work ability, low life satisfaction and a reduced level of aerobic capacity. In the final logistic regression model (Nagelkerke R Square 0.296, p < 0.001), poor work ability was the most important factor for perceiving low satisfaction with life (Odds ratio 3.369, 95% CI 2.040-5.565, p < 0.001, Nagelkerke R Square 0.177). Reduced aerobic capacity, fatigue and living in a city also increased the odds of low life satisfaction. As people with post-COVID-19 report several long-term consequences, this suggests that there is a need for targeted care for this group. The results of this study can serve as guidance for healthcare authorities regarding important long-term consequences that should be considered in rehabilitation programs directed toward post-COVID-19.

Post-COVID syndrome (PCS) is a medical condition characterized by the persistence of a wide range of symptoms after acute infection by SARS-CoV-2. The work capacity consequences of this disorder have scarcely been studied. We aimed to analyze the factors associated with occupational status in patients with PCS. This cross-sectional study involved 77 patients with PCS on active work before SARS-CoV-2 infection. Patients were evaluated 20.71 ± 6.50 months after clinical onset. We conducted a survey on occupational activity and cognitive and clinical symptoms. The association between occupational activity and fatigue, depression, anxiety, sleep quality, and cognitive testing was analyzed. Thirty-eight (49.4%) patients were working, and thirty-nine (50.6%) patients were not. Of those not working at the moment of the assessment, 36 (92.3%) patients were on sick leave. In 63 patients (81.8% of the sample), sick leave was needed at some point due to PCS. The mean duration of sick leave was 12.07 ± 8.07 months. According to the patient's perspective, the most disabling symptoms were cognitive complaints (46.8%) and fatigue (31.2%). Not working at the moment of the assessment was associated with higher levels of fatigue and lower cognitive performance in the Stroop test. No association was found between occupational status with depression and anxiety questionnaires. Our study found an influence of PCS on work capacity. Fatigue and cognitive issues were the most frequent symptoms associated with loss of work capacity.

The coronavirus disease 2019 (COVID-19) is still in a global pandemic state. Some studies have reported that COVID-19 vaccines had a protective effect against long COVID. However, the conclusions of the studies on the effect of COVID-19 vaccines on long COVID were not consistent. This study aimed to systematically review relevant studies in the real world, and performed a meta-analysis to explore the relationship between vaccination and long COVID. We systematically searched PubMed, Embase, Web of science, and ScienceDirect from inception to 19 September 2022. The PICO (P: patients; I: intervention; C: comparison; O: outcome) was as follows: patients diagnosed with COVID-19 (P); vaccination with COVID-19 vaccines (I); the patients were divided into vaccinated and unvaccinated groups (C); the outcomes were the occurrence of long COVID, as well as the various symptoms of long COVID (O). A fixed-effect model and random-effects model were chosen based on the heterogeneity between studies in order to pool the effect value. The results showed that the vaccinated group had a 29% lower risk of developing long COVID compared with the unvaccinated group (RR = 0.71, 95% CI: 0.58-0.87, p < 0.01). Compared with patients who were not vaccinated, vaccination showed its protective effect in patients vaccinated with two doses (RR = 0.83, 95% CI: 0.74-0.94, p < 0.01), but not one dose (RR = 0.83, 95% CI: 0.65-1.07, p = 0.14). In addition, vaccination was effective against long COVD in patients either vaccinated before SARS-CoV-2 infection/COVID-19 (RR = 0.82, 95% CI: 0.74-0.91, p < 0.01) or vaccinated after SARS-CoV-2 infection/COVID-19 (RR = 0.83, 95% CI: 0.74-0.92, p < 0.01). For long COVID symptoms, vaccination reduced the risk of cognitive dysfunction/symptoms, kidney diseases/problems, myalgia, and sleeping disorders/problems sleeping. Our study shows that COVID-19 vaccines had an effect on reducing the risk of long COVID in patients vaccinated before or after SARS-CoV-2 infection/COVID-19. We suggest that the vaccination rate should be improved as soon as possible, especially for a complete vaccination course. There should be more studies to explore the basic mechanisms of the protective effect of COVID-19 vaccines on long COVID in the future.

The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited.

. Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry.

Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on 'naïve', CM, EM4, and pE1 2-3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients.

We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on 'naïve' and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response.