Initial Infection Research Articles

The host transcriptional response to superinfection by influenza A virus and Streptococcus pneumoniae.

Secondary bacterial infections are the most frequent complications during influenza A virus (IAV) pandemic outbreaks, contributing to excessive morbidity and mortality in the human population. Most IAV-related deaths are attributed to Streptococcus pneumoniae (SP) infections, which usually begin within the first week of IAV infection in the respiratory tracts. Here, we focused on longitudinal transcriptional responses during a superinfection model consisting of an SP infection that follows an initial IAV infection, comparing superinfection to an IAV-only infection, an SP-only infection, and control treatments. Our longitudinal data allowed a fine analysis of gene expression changes during superinfection. For instance, we found that superinfected mice exhibited rapid gene expression induction or reduction within the first 12 h after encountering the second pathogen. Cell proliferation and immune response activation processes were upregulated, while endothelial processes, vasculogenesis, and angiogenesis were downregulated, providing promising targets for future therapeutic interventions. We further analyzed the longitudinal transcriptional responses in the context of a previously defined spectrum of the host's resistance state, revealing superinfection-specific reprogramming of resistance states, such as reprogramming of fatty acid metabolism and interferon signaling. The reprogrammed functions are compelling new targets for switching the pathogenic superinfection state into a single-infection state.

Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy.

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) remains a threat to pregnant women. However, the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood. Here, we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy. Compared to control placentas, SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection. However, subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface. Notably, the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester. Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.

Advanced magnetic resonance neuroimaging techniques: feasibility and applications in long or post-COVID-19 syndrome - a review.

Long-term or post-COVID-19 syndrome (PCS) is a condition that affects people infected with SARS‑CoV‑2, the virus that causes COVID-19. PCS is characterized by a wide range of persistent or new symptoms that last months after the initial infection, such as fatigue, shortness of breath, cognitive dysfunction, and pain. Advanced magnetic resonance (MR) neuroimaging techniques can provide valuable information on the structural and functional changes in the brain associated with PCS as well as potential biomarkers for diagnosis and prognosis. In this review, we discuss the feasibility and applications of various advanced MR neuroimaging techniques in PCS, including perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), functional MR imaging (fMRI), diffusion tensor imaging (DTI), and tractography. We summarize the current evidence on neuroimaging findings in PCS, the challenges and limitations of these techniques, and the future directions for research and clinical practice. Although still uncertain, advanced MRI techniques show promise for gaining insight into the pathophysiology and guiding the management of COVID-19 syndrome, pending larger validation studies.

Guardians of immunity: NK cell-mediated defense in COVID-19 and post-COVID scenarios.

The COVID-19 pandemic has left a lasting impact on global health, challenging communities, healthcare systems, and researchers worldwide. As we navigate this unprecedented crisis, this paper embarks on a multifaceted exploration of the pivotal role played by natural killer (NK) cells in the context of COVID-19. A significant portion of this paper is devoted to dissecting the nuanced role that NK cells assume in the context of COVID-19. From the initial acute infection to post-recovery immunity, NK cells emerge as critical players. We scrutinize the activation and dysregulation of NK cells during SARS-CoV-2 infection, shedding light on their potential contribution to disease severity. Moreover, we explore the fascinating landscape of post-COVID immunity, where NK cells are known to interact with adaptive immune responses, providing a foundation for long-term protection. In light of their central role, we investigate therapeutic strategies targeting NK cells in COVID-19 management, presenting an overview of current research efforts and their promise in mitigating disease progression. Lastly, we draw attention to research gaps, emphasizing the need for further investigation into NK cell dynamics during COVID-19. These gaps represent opportunities for advancing our understanding of NK cell biology and, by extension, enhancing our strategies for combating this global health crisis. This comprehensive exploration not only highlights the intricate interplay between NK cells and the COVID-19 pandemic but also underscores the importance of these innate immune warriors in shaping both the acute response and long-term immunity, ultimately contributing to the broader discourse surrounding the pandemic's pathophysiology and therapeutic approaches.

Enhancement of broad-spectrum disease resistance in wheat through key genes involved in systemic acquired resistance.

Systemic acquired resistance (SAR) is an inducible disease resistance phenomenon in plant species, providing plants with broad-spectrum resistance to secondary pathogen infections beyond the initial infection site. In Arabidopsis, SAR can be triggered by direct pathogen infection or treatment with the phytohormone salicylic acid (SA), as well as its analogues 2,6-dichloroisonicotinic acid (INA) and benzothiadiazole (BTH). The SA receptor non-expressor of pathogenesis-related protein gene 1 (NPR1) protein serves as a key regulator in controlling SAR signaling transduction. Similarly, in common wheat (Triticum aestivum), pathogen infection or treatment with the SA analogue BTH can induce broad-spectrum resistance to powdery mildew, leaf rust, Fusarium head blight, and other diseases. However, unlike SAR in the model plant Arabidopsis or rice, SAR-like responses in wheat exhibit unique features and regulatory pathways. The acquired resistance (AR) induced by the model pathogen Pseudomonas syringae pv. tomato strain DC3000 is regulated by NPR1, but its effects are limited to the adjacent region of the same leaf and not systemic. On the other hand, the systemic immunity (SI) triggered by Xanthomonas translucens pv. cerealis (Xtc) or Pseudomonas syringae pv. japonica (Psj) is not controlled by NPR1 or SA, but rather closely associated with jasmonate (JA), abscisic acid (ABA), and several transcription factors. Furthermore, the BTH-induced resistance (BIR) partially depends on NPR1 activation, leading to a broader and stronger plant defense response. This paper provides a systematic review of the research progress on SAR in wheat, emphasizes the key regulatory role of NPR1 in wheat SAR, and summarizes the potential of pathogenesis-related protein (PR) genes in genetically modifying wheat to enhance broad-spectrum disease resistance. This review lays an important foundation for further analyzing the molecular mechanism of SAR and genetically improving broad-spectrum disease resistance in wheat.

Describing the Lived Experience and Resource Needs of Individuals With Long COVID.

Individuals with long COVID report diverse symptoms lasting weeks or months after initial infection, causing significant psychosocial distress. Navigating health care interactions are often difficult for these individuals due to the diffuse nature of their symptoms, a lack of effective treatment options, and skepticism from some providers. To better understand these challenges, this study sought to further describe the lived experience of individuals with long COVID. A survey was conducted with individuals evaluated for long COVID at a specialty clinic (n = 200), which included questions about prior conditions, symptoms, use of medical and support services, and information and resource needs. Participants reported a mean of 10.75 persistent symptoms, the most common being fatigue and difficulty concentrating, with broad effects on daily functioning. Participants saw a mean of 5.92 providers for treatment of their symptoms, and 88.5% identified health care providers as a trusted source of information. Interest in research findings (60.5%) and opportunities for participation (47.5%) were moderate and varied by COVID vaccination status. Unvaccinated individuals (n = 27) also reported less trust in government sources of information, less college education, lower household income, and greater likelihood of having public insurance. Our findings suggest that individuals with long COVID experience many ongoing and complex symptoms with diverse effects on daily living; that health care providers are an important source for public health messaging about long COVID; and that unvaccinated individuals are likely to have differing needs and receptiveness to information than vaccinated individuals with long COVID.

Unraveling Links between Chronic Inflammation and Long COVID: Workshop Report.

As COVID-19 continues, an increasing number of patients develop long COVID symptoms varying in severity that last for weeks, months, or longer. Symptoms commonly include lingering loss of smell and taste, hearing loss, extreme fatigue, and "brain fog." Still, persistent cardiovascular and respiratory problems, muscle weakness, and neurologic issues have also been documented. A major problem is the lack of clear guidelines for diagnosing long COVID. Although some studies suggest that long COVID is due to prolonged inflammation after SARS-CoV-2 infection, the underlying mechanisms remain unclear. The broad range of COVID-19's bodily effects and responses after initial viral infection are also poorly understood. This workshop brought together multidisciplinary experts to showcase and discuss the latest research on long COVID and chronic inflammation that might be associated with the persistent sequelae following COVID-19 infection.

Review of Related Factors for Persistent Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated.

How does COVID-19 vaccination affect long-COVID symptoms?

The current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition. This was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate. In total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) who received at least one dose of any vaccine had long long- COVID symptoms (p = 0.032). In people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. However, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.

Does the resumption of international tourism heighten COVID-19 transmission?

Reopening countries also carries the risk of another wave of infections in many parts of the world, raising the question of whether we are ready to reopen our countries. This study examines the impact of reopening countries to receive foreign tourists on the spread of COVID-19 in 2022, encompassing 83 countries worldwide. We employ spatial quantile models capable of analyzing the spatial impact of tourism on the spread of the virus at different quantile levels. The research categorizes countries into three groups: low infection rate (10th-30th quantiles), moderate infection rate (40th-60th quantiles), and high infection rate (70th-90th quantiles). This allows for a more comprehensive and detailed comparison of the impacts. Additionally, considering the spatial dimension enables the explanation of both the direct and indirect effects of tourists on the country itself and neighboring countries. The findings reveal that the number of international tourists has a significant effect on the COVID-19 infection rate, particularly in countries with high initial infection rates. However, countries that effectively controlled their infection rates at a low level could maintain a low infection rate even after reopening to foreign tourists. It is also observed that reopening a country's borders negatively impacts the infection rate of neighboring countries. These important findings imply that governments of highly infected countries should shift their focus towards bolstering their economy by promoting domestic tourism and should delay reopening until the number of infections decreases.

Skin muscle is the initial site of viral replication for arboviral bunyavirus infection

The first step in disease pathogenesis for arboviruses is the establishment of infection following vector transmission. For La Crosse virus (LACV), the leading cause of pediatric arboviral encephalitis in North America, and other orthobunyaviruses, the initial course of infection in the skin is not well understood. Using an intradermal (ID) model of LACV infection in mice, we find that the virus infects and replicates nearly exclusively within skin-associated muscle cells of the panniculus carnosus (PC) and not in epidermal or dermal cells like most other arbovirus families. LACV is widely myotropic, infecting distal muscle cells of the peritoneum and heart, with limited infection of draining lymph nodes. Surprisingly, muscle cells are resistant to virus-induced cell death, with long term low levels of virus release progressing through the Golgi apparatus. Thus, skin muscle may be a key cell type for the initial infection and spread of arboviral orthobunyaviruses.

Role of IgG avidity in eyes with active Toxoplasma retinochoroiditis.

To study the role of Toxoplasma IgG avidity in evaluating the stage of systemic infection during manifestation as toxoplasma retinochoroiditis and its clinical implications in eastern India. Retrospective chart review of Toxoplasma retinochoroiditis cases with Toxoplasma serology for IgG, IgM, and IgG avidity. Included in this study were 17 eyes of 17 patients who had active retinitis located in the macula (14), mid-periphery (2), or periphery (1). They were either primary lesions (12) or reactivations (5). All the cases had Toxoplasma IgG positive; one case had IgM positivity, while all the cases had high IgG avidity values. IgG avidity had a positive correlation with the duration of symptoms. We observed high IgG avidity values in active retinochoroiditis in both primary ocular Toxoplasmosis and reactivation subgroups. These results indicate a late ocular manifestation after initial systemic infection with a possible incubation period ranging from 5 weeks to 5 months.

Sleep quality among non-hospitalized COVID-19 survivors: a national cross-sectional study.

Insomnia is a common symptom after COVID-19 infection; however, its current evidence was among hospitalized COVID-19 patients. This study aimed to assess the prevalence of insomnia and identify its association with depression and anxiety among non-hospitalized COVID-19 recovered population. We conducted a cross-sectional online survey of 1,056 COVID-19 survivors within 6 months of initial COVID-19 infection and retrieved did not require hospitalization. The Insomnia Severity Index, and Depression Anxiety and Stress Scale-14 were used. Multivariate logistic regression was used to examine the associations between depressive and anxiety score, and participants' insomnia level. The prevalence of insomnia was 76.1%, and among those, 22.8% of participants scored for severe insomnia. One third of participants reported worse sleep quality, shorter sleep duration, and harder to fall asleep, half reported more awaken nights after COVID-19 infection. Participants with depressive (OR 3.45; 95%CI 1.87-6.34) or anxiety (OR 3.93; 95%CI 2.52-6.13) had significantly higher odds of developing insomnia. Other risk factors of insomnia included pre-existing chronic conditions and higher education level, while COVID-19 symptoms and duration were not significantly associated. Our study highlights the substantial burden of insomnia among non-hospitalized COVID-19 survivors and the significant association of depression and anxiety on the development of this long-term effect of COVID-19. These findings underscore the need for comprehensive interventions that address both sychological and sleeping health in this population.

Safety and efficiency of COVID-19 vaccine in North Africa

ABSTRACT Background In the absence of a specific treatment for COVID-19, preventive measures have been implemented to control this pandemic and vaccination is one of them. However, it is crucial to verify the safety and efficiency of every vaccine. The aim was to determinate the predictive factors of side effects and reinfection after COVID-19 vaccine. Methods A cross-sectional study was conducted in February 2022 among Tunisians infected with COVID-19 between March 2020 and February 2022, using an online self-administered questionnaire. We conducted univariate and multivariate analyses using binary stepwise logistic regression. Results A total of 1541 was selected from 1911 individuals. Comorbidities affected a quarter of the population (22.3%). Before the initial infection, 39.3% had received full vaccination, and 8.7% had received partial vaccination. By February 2022, the majority (82.9%) had received at least two vaccine doses. The reinfection rate was 30.6%. All vaccines prior to the first infection was identified as a protective factor against reinfection. Inactivated virus vaccinations were less likely to induce adverse effects. Conclusion ach vaccine has its own set of advantages and disadvantages: mRNA-based vaccines had a higher incidence of side effects but all vaccines provided better protection against reinfection.

Enhancing detection of SARS-CoV-2 re-infections using longitudinal sero-monitoring: demonstration of a methodology in a cohort of people experiencing homelessness in Toronto, Canada

BackgroundAccurate estimation of SARS-CoV-2 re-infection is crucial to understanding the connection between infection burden and adverse outcomes. However, relying solely on PCR testing results in underreporting. We present a novel approach that includes longitudinal serologic data, and compared it against testing alone among people experiencing homelessness.MethodsWe recruited 736 individuals experiencing homelessness in Toronto, Canada, between June and September 2021. Participants completed surveys and provided saliva and blood serology samples every three months over 12 months of follow-up. Re-infections were defined as: positive PCR or rapid antigen test (RAT) results > 90 days after initial infection; new serologic evidence of infection among individuals with previous infection who sero-reverted; or increases in anti-nucleocapsid in seropositive individuals whose levels had begun to decrease.ResultsAmong 381 participants at risk, we detected 37 re-infections through PCR/RAT and 98 re-infections through longitudinal serology. The comprehensive method identified 37.4 re-infection events per 100 person-years, more than four-fold more than the rate detected through PCR/RAT alone (9.0 events/100 person-years). Almost all test-confirmed re-infections (85%) were also detectable by longitudinal serology.ConclusionsLongitudinal serology significantly enhances the detection of SARS-CoV-2 re-infections. Our findings underscore the importance and value of combining data sources for effective research and public health surveillance.

Post-COVID in women after SARS-CoV-2 infection during pregnancy - a pilot study with follow-up data from the COVID-19-related Obstetric and Neonatal Outcome Study (CRONOS).

Pregnant women are at an increased risk of severe COVID-19 and adverse pregnancy outcomes; data on maternal long-term outcome is scarce. We analyzed long-term follow-ups on women who experienced a SARS-CoV-2 infection during pregnancy to evaluate post-COVID symptoms, particularly fatigue, and their association with quality of life (QoL). 773 women who enrolled in the CRONOS registry between April 2020 and August 2021 were contacted for follow-up from December 2022 to April 2023. Data was gathered through a web-based questionnaire. Subsequently, study coordinators matched the follow-up data with the existing CRONOS data. 110/773 (14%) women provided data. 20.9% experienced only acute symptoms during their SARS-CoV-2 infection in pregnancy, while 2.7% women experienced symptoms lasting longer than 4 weeks (long COVID). Symptoms lasting longer than 12 weeks (post-COVID) were reported by 63.6% women and occurred more often after severe COVID-19. Fatigue was the most frequently reported symptom (88%), with 55% of women still experiencing it more than one year after initial infection. 76% of women rated their QoL as "good" or "very good". Women experiencing post-COVID reported a significantly lower QoL. This is the first German long-term data on women after SARS-CoV-2 infection during pregnancy, showing a high rate of post-COVID, a persistence of fatigue, and the impact on QoL. Continuous monitoring of pregnant women with COVID-19 is needed to develop comprehensive management strategies.

Long-term outcomes after COVID-19 infection in transplant recipients.

Long-term outcomes after COVID-19 infection unique to solid organ transplant recipients (SOTR) are not published. We describe outcomes including readmission, allograft rejection, allograft dysfunction, allograft failure, and death. We conducted a retrospective cohort study of mostly unvaccinated SOTR with COVID-19 from March 2020 to November 2021. Disease severity was assigned by NIH criteria. Data included demographics, clinical features, treatment, and outcomes and are presented as mean±standard deviation or median (range). One hundred and thirty-eight SOTR were diagnosed with COVID-19 at a median of 5 (IQR 3-8) years post-transplant with a mean age of 57±12years at diagnosis. Forty-one recovered at home; 97 were admitted. 12/32 (37.5%) SOTR with critical disease expired during initial admission. Among those who recovered, 48/126 (38.0%) had asymptomatic or mild infection, 31/126 (24.6%) had moderate, 27/126 (21.4%) severe, and 20/126 (15.9%) critical infection. 38/85 (44.7%) of SOTR who survived initial admission had 74 readmissions within 180days (Figure 1). The 6-month mortality rate among those who survived infection was 4/126 (3.2%). The mean time from initial infection to death was 32±66days in inpatient deaths and 95±39days in those who were discharged or never admitted. Six-month graft dysfunction occurred in 18/125 (14.4%) and graft failure in 9/126 (7.2%); five failures were deaths with function. Readmissions after COVID-19 infection were frequent after the index admission. Rejection was relatively infrequent; graft dysfunction at 6months post-infection was more common than rejection. Six-month mortality following COVID-19 recovery in SOTR was significant; close follow-up of patients is warranted.

Early-life pulmonary viral infection leads to long-term functional and lower airway structural changes in the lungs.

Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life. Our data demonstrate that early-life RSV infection modifies lung structure, leading to decreased lung function. At 5 wk postneonatal RSV infection, significant defects are observed in baseline pulmonary function test (PFT) parameters consistent with decreased lung function as well as enlarged alveolar spaces. Lung function changes in the early-life RSV-infected group continue at 3 mo of age. The altered PFT and structural changes induced by early-life RSV were mitigated in TSLPR-/- mice that have previously been shown to have reduced immune cell accumulation associated with a persistent Th2 environment. Importantly, long-term effects were demonstrated using a secondary RSV infection 3 mo following the initial early-life RSV infection and led to significant additional defects in lung function, with severe mucus deposition within the airways, and consolidation of the alveolar spaces. These studies suggest that early-life respiratory viral infection leads to alterations in lung structure/repair that predispose to diminished lung function later in life.NEW & NOTEWORTHY These studies outline a novel finding that early-life respiratory virus infection can alter lung structure and function long-term. Importantly, the data also indicate that there are critical links between inflammatory responses and subsequent events that produce a more severe pathogenic response later in life. The findings provide additional data to support that early-life infections during lung development can alter the trajectory of airway function.

Msp1, msp2, and glurp genotyping to differentiate Plasmodium falciparum recrudescence from reinfections during prevention of reestablishment phase, Sri Lanka, 2014–2019

BackgroundSri Lanka after eliminating malaria in 2012, is in the prevention of re-establishment (POR) phase. Being a tropical country with high malariogenic potential, maintaining vigilance is important. All malaria cases are investigated epidemiologically and followed up by integrated drug efficacy surveillance (iDES). Occasionally, that alone is not adequate to differentiate Plasmodium falciparum reinfections from recrudescences. This study evaluated the World Health Organization and Medicines for Malaria Venture (MMV) recommended genotyping protocol for the merozoite surface proteins (msp1, msp2) and the glutamate-rich protein (glurp) to discriminate P. falciparum recrudescence from reinfection in POR phase.MethodsAll P. falciparum patients detected from April 2014 to December 2019 were included in this study. Patients were treated and followed up by iDES up to 28 days and were advised to get tested if they develop fever at any time over the following year. Basic socio-demographic information including history of travel was obtained. Details of the malariogenic potential and reactive entomological and parasitological surveillance carried out by the Anti Malaria Campaign to exclude the possibility of local transmission were also collected. The msp1, msp2, and glurp genotyping was performed for initial and any recurrent infections. Classification of recurrent infections as recrudescence or reinfection was done based on epidemiological findings and was compared with the genotyping outcome.ResultsAmong 106 P. falciparum patients, six had recurrent infections. All the initial infections were imported, with a history of travel to malaria endemic countries. In all instances, the reactive entomological and parasitological surveillance had no evidence for local transmission. Five recurrences occurred within 28 days of follow-up and were classified as recrudescence. They have not travelled to malaria endemic countries between the initial and recurrent infections. The other had a recurrent infection after 105 days. It was assumed a reinfection, as he had travelled to the same malaria endemic country in between the two malaria attacks. Genotyping confirmed the recrudescence and the reinfection.ConclusionsThe msp1, msp2 and glurp genotyping method accurately differentiated reinfections from recrudescence. Since reinfection without a history of travel to a malaria endemic country would mean local transmission, combining genotyping outcome with epidemiological findings will assist classifying malaria cases without any ambiguity.

The association between Long-COVID symptomology, perceived symptom burden and mental health in COVID-19 patients in Shijiazhuang, China: a population-based health survey.

Long-COVID (LC) refers to post-acute COVID-19 symptoms that can last for months or longer after the initial infection, affecting the physical health of infected patients. This study aims to investigate the association between the symptomology of LC and the mental health of patients in China. It also aims to examine the relationship between the perceived symptom burden and mental health of these patients. A population-based stratified cluster sample was recruited, using a standard sampling procedure, from a prefecture-level city in Northern China. Participants included patients who had tested positive for COVID-19 after December 2022. LC symptomology was assessed using a LC symptoms checklist where the perceived symptom burden was measured by the included 5-point Likert scales. Mental health of patients was measured using the Depression, Anxiety, and Stress Scale (DASS), the original Connor-Davidson Resilience Scale (CD-RISC), and the Duke-UNC Functional Social Support Questionnaire (DUFSS). Data were analysed using multiple linear regression models. About 25% of respondents, experienced COVID symptoms lasting longer than two months that could only be explained by the infection. Post-exertional malaise (22.2%) and fatigue (21.2%) were the most common symptoms. After controlling for potential confounding variables, LC symptomology was significantly and positively associated with depression (t=2.09, p=0.037) and anxiety (t=4.51, p<0.001), but not stress. Perceived symptoms burden was also positively and significantly related to depression (β=0.35, p<0.001), anxiety (β=0.54, p<0.001), and stress (β=0.35, p<0.001), suggesting a dose-response relationship between perceived symptom burden and mental ill health. This study highlights the importance of recognising the risk of LC, patients' perception of the symptom burden and its potential impact on mental health. Healthcare professionals should be aware of the complexity of psychological comorbidities among infected patients reporting prolonged symptoms, and be able to give advice regarding long-term management of the symptoms.