Symptom Burden among Older COVID-19 Survivors Two Years after Hospital Discharge.

To study the long-term symptom burden among older COVID-19 survivors 2 years after hospital discharge and identify associated risk factors. The current cohort study included COVID-19 survivors aged 60 years and above, who were discharged between February 12 and April 10, 2020, from two designated hospitals in Wuhan, China. All patients were contacted via telephone and completed a standardized questionnaire assessing self-reported symptoms, the Checklist Individual Strength (CIS)-fatigue subscale, and two subscales of the Hospital Anxiety and Depression Scale (HADS). Of the 1,212 patients surveyed, the median (IQR) age was 68.0 (64.0-72.0), and 586 (48.3%) were male. At the two-year follow-up, 259 patients (21.4%) still reported at least one symptom. The most frequently self-reported symptoms were fatigue, anxiety, and dyspnea. Fatigue or myalgia, which was the most common symptom cluster (11.8%; 143/1212), often co-occurred with anxiety and chest symptoms. A total of 89 patients (7.7%) had CIS-fatigue scores ≥ 27, with older age (odds ratio [OR], 1.08; 95% CI: 1.05-1.11, P < 0.001) and oxygen therapy (OR, 2.19; 95% CI: 1.06-4.50, P= 0.03) being risk factors. A total of 43 patients (3.8%) had HADS-Anxiety scores ≥ 8, and 130 patients (11.5%) had HADS-Depression scores ≥ 8. For the 59 patients (5.2%) who had HADS total scores ≥ 16, older age, serious illness during hospitalization and coexisting cerebrovascular diseases were risk factors. Cooccurring fatigue, anxiety, and chest symptoms, as well as depression, were mainly responsible for long-term symptom burden among older COVID-19 survivors 2 years after discharge.

Early Identification of Crop Type for Smallholder Farming Systems Using Deep Learning on Time-Series Sentinel-2 Imagery.

Climate change and the COVID-19 pandemic have disrupted the food supply chain across the globe and adversely affected food security. Early estimation of staple crops can assist relevant government agencies to take timely actions for ensuring food security. Reliable crop type maps can play an essential role in monitoring crops, estimating yields, and maintaining smooth food supplies. However, these maps are not available for developing countries until crops have matured and are about to be harvested. The use of remote sensing for accurate crop-type mapping in the first few weeks of sowing remains challenging. Smallholder farming systems and diverse crop types further complicate the challenge. For this study, a ground-based survey is carried out to map fields by recording the coordinates and planted crops in respective fields. The time-series images of the mapped fields are acquired from the Sentinel-2 satellite. A deep learning-based long short-term memory network is used for the accurate mapping of crops at an early growth stage. Results show that staple crops, including rice, wheat, and sugarcane, are classified with 93.77% accuracy as early as the first four weeks of sowing. The proposed method can be applied on a large scale to effectively map crop types for smallholder farms at an early stage, allowing the authorities to plan a seamless availability of food.

Clinical characteristics and risk factors for a prolonged length of stay of patients with asymptomatic and mild COVID-19 during the wave of Omicron from Shanghai, China.

BACKGROUND: This study aims to investigate the clinical characteristics and the length of hospital stay (LOS), as well as risk factors for prolonged LOS in a cohort of asymptomatic and mild COVID-19 patients infected with the Omicron variant. METHODS: A total of 1166 COVID-19 patients discharged from the inpatient ward of the largest makeshift hospital (May 8-10, 2022) in Shanghai, China, were included. The demographics, medical history, and the lowest and admission cycle threshold (Ct) values of the RT-PCR tests for SARS-CoV-2 genes of the open reading frame 1ab (Ct-ORF) and the nucleocapsid protein (Ct-N) during hospitalization were recorded. Patients with LOS > 7 days, or LOS ≤ 7 days were included in the Prolonged group or the Control group, separately. The clinical characteristics and LOS of the participants in the two groups were described and compared. Multivariate Logistic and linear regression analyses were applied to explore the risk factors for prolonged LOS. The diagnostic efficacy of the lowest and admission Ct values for the Prolonged group was tested via the receiver operating characteristic (ROC) curve analysis. RESULTS: The median LOS was 6 days in the total study population. The age was older (45.52 ± 14.78 vs. 42.54 ± 15.30, P = 0.001), while both the lowest and admission Ct-ORF (27.68 ± 3.88 vs. 37.00 ± 4.62, P < 0.001; 30.48 ± 5.03 vs. 37.79 ± 3.81, P < 0.001) and Ct-N (25.79 ± 3.60 vs. 36.06 ± 5.39, P < 0.001; 28.71 ± 4.95 vs. 36.95 ± 4.59, P < 0.001) values were significantly lower in the Prolonged group. There were more mild cases in the Prolonged group (23.8% vs. 11.5%, P < 0.001). The symptom spectrum differed between the two groups. In multivariate analyses, age, disease category, and the lowest Ct-N values were shown to be associated with prolonged LOS. Besides, both the lowest and admission Ct-ORF (AUC = 0.911 and 0.873) and Ct-N (AUC = 0.912 and 0.874) showed robust diagnostic efficacy for prolonged LOS. CONCLUSIONS: Our study firstly reports the clinical characteristics and risk factors for prolonged LOS during the wave of the Omicron epidemic in Shanghai, China. These findings provide evidence for the early identification of asymptomatic and mild COVID-19 patients at a high risk of prolonged hospitalization who may require early intervention, and long-term monitoring and management.

Development of receptor binding domain-based double-antigen sandwich lateral flow immunoassay for the detection and evaluation of SARS-CoV-2 neutralizing antibody in clinical sera samples compared with the conventional virus neutralization test.

Vaccination is an effective strategy to fight COVID-19. However, the effectiveness of the vaccine varies among different populations in varying immune effects. Neutralizing antibody (NAb) level is an important indicator to evaluate the protective effect of immune response after vaccination. Lateral flow immunoassay (LFIA) is a rapid, safe and sensitivity detection method, which has great potential in the detection of SARS-CoV-2 NAb. In this study, a fluorescent beads-based lateral flow immunoassay (FBs-LFIA) and a latex beads-based LFIA (LBs-LFIA) using double antigen sandwich (DAS) strategy were established to detect NAbs in the serum of vaccinated people. The limit of detection (LoD) of the FBs-LFIA was 1.13 ng mL- 1 and the LBs-LFIA was 7.11 ng mL- 1. The two LFIAs were no cross-reactive with sera infected by other pathogenic bacteria. Furthermore, the two LFIAs showed a good performance in testing clinical samples. The sensitivity of FBs-LFIA and LBs-LFIA were 97.44% (95%CI: 93.15%-99.18%) and 98.29% (95%CI: 95.84%-99.37%), and the specificity were 98.28% (95%CI: 95.37%-99.45%) and 97.70% (95%CI: 94.82%-99.06%) compared with the conventional virus neutralization test (cVNT), respectively. Notably, the LBs-LFIA was also suitable for whole blood sample, requiring only 3 µL of whole blood, which provided the possibility to detect NAbs at home. To sum up, the two LFIAs based on double antigen sandwich established by us can rapidly, safely, sensitively and accurately detect SARS-CoV-2 NAb in human serum.

IL-6 drives T cell death to participate in lymphopenia in COVID-19.

Lymphopenia is a common observation in patients with COVID-19. To explore the cause of T cell lymphopenia in the disease, laboratory results of 64 hospitalized COVID-19 patients were retrospectively analyzed and six patients were randomly selected to trace their changes of T lymphocytes and plasma concentration of IL-6 for the course of disease. Results confirmed that the T-cell lymphopenia, especially CD4+ T cell reduction in COVID-19 patients, was a reliable indicator of severity and hospitalization in infected patients. And CD4+ T cell count below 200 cells/µL predicts critical illness in COVID-19 patients. In vitro assay supported that exposure to key contributors (IL-1ß, IL-6, TNF-α and IFN-γ) of COVID-19 cytokine storm caused substantial death of activated T cells. Among these contributors, IL-6 level was found to probably reversely correlate with T cell counts in patients. And IL-6 alone was potent to induce T cell reduction by gasderminE-mediated pyroptosis, inferring IL-6 took a part in affecting the function and status of T cells in COVID-19 patients. Intervention of IL-6 mediated T cell pryprotosis may effectively delay disease progression, maintain normal immune status at an early stage of infection.

Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China.

Importance: Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness. Objective: To assess the health outcomes among hospitalized COVID-19 survivors over 2 years and to identify factors associated with increased risk of persistent symptoms. Design, Setting, and Participants: This was a longitudinal cohort study of patients who survived COVID-19 at 2 COVID-19-designated hospitals in Wuhan, China, from February 12 to April 10, 2020. All patients were interviewed via telephone at 1 year and 2 years after discharge. The 2-year follow-up study was conducted from March 1 to April 6, 2022. Statistical analysis was conducted from April 20 to May 5, 2022. The severity of disease was defined by World Health Organization guideline for COVID-19. Exposures: COVID-19. Main Outcomes and Measures: The main outcome was symptom changes over 2 years after hospital discharge. All patients completed a symptom questionnaire for evaluation of symptoms, along with a chronic obstructive pulmonary disease assessment test (CAT) at 1-year and 2-year follow-up visits. Results: Of 3988 COVID-19 survivors, a total of 1864 patients (median [IQR] age, 58.5 [49.0-68.0] years; 926 male patients [49.7%]) were available for both 1-year and 2-year follow-up visits. The median (IQR) time from discharge to follow-up at 2 years was 730 (719-743) days. At 2 years after hospital discharge, 370 patients (19.8%) still had symptoms, including 224 (12.0%) with persisting symptoms and 146 (7.8%) with new-onset or worsening of symptoms. The most common symptoms were fatigue, chest tightness, anxiety, dyspnea, and myalgia. Most symptoms resolved over time, but the incidence of dyspnea showed no significant change (1-year vs 2-year, 2.6% [49 patients] vs 2.0% [37 patients]). A total of 116 patients (6.2%) had CAT total scores of at least 10 at 2 years after discharge. Patients who had been admitted to the intensive care unit had higher risks of persistent symptoms (odds ratio, 2.69; 95% CI, 1.02-7.06; P = .04) and CAT scores of 10 or higher (odds ratio, 2.83; 95% CI, 1.21-6.66; P = .02). Conclusions and Relevance: In this cohort study, 2 years after hospital discharge, COVID-19 survivors had a progressive decrease in their symptom burden, but those with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms. These results are related to the original strain of the virus, and their relevance to infections with the Omicron variant is not known.

Sars-Cov-2 Spike Protein-Induced Damage of hiPSC-Derived Cardiomyocytes.

Sars-Cov-2 may trigger molecular and functional alterations of cardiomyocytes (CMs) of the heart due to the presence of receptor angiotensin-converting enzyme 2 (ACE2) of the host cells. While the endocytic itinerary of the virus via cleavage of the spike protein of Sars-Cov-2 is well understood, the role of the remaining part of the spike protein subunit and ACE2 complex is still elusive. Herein, the possible effects of this complex are investigated by using synthetic spike proteins of Sars-Cov-2, human-induced pluripotent stem cells (hiPSC), and a culture device made of an arrayed monolayer of cross-linked nanofibers. hiPSCs are first differentiated into CMs that form cardiac tissue-like constructs with regular beating and expression of both ACE2 and gap junction protein Connexin 43. When incubated with the spike proteins, the hiPSC-CMs undergo a rhythmic fluctuation with overstretched sarcomere structures and dispersed gap junction proteins. When incubated with the spike proteins and supplementary angiotensin II, the damage of the spike protein on hiPSC-CMs is enhanced due to downregulated ACE2, chromatin margination, altered Connexin 43 expression, sarcomere disruption, and beating break. This discovery may imply latent effects of the spike proteins on the heart.

Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China.

Importance: The long-term health outcomes and symptom burden of COVID-19 remain largely unclear. Objective: To evaluate health outcomes of COVID-19 survivors 1 year after hospital discharge and to identify associated risk factors. Design, Setting, and Participants: This retrospective, multicenter cohort study was conducted at 2 designated hospitals, Huoshenshan Hospital and Taikang Tongji Hospital, both in Wuhan, China. All adult patients with COVID-19 discharged between February 12 and April 10, 2020, were screened for eligibility. Of a consecutive sample of 3988 discharged patients, 1555 were excluded (796 declined to participate and 759 were unable to be contacted) and the remaining 2433 patients were enrolled. All patients were interviewed via telephone from March 1 to March 20, 2021. Statistical analysis was performed from March 28 to April 18, 2021. Exposures: COVID-19. Main Outcomes and Measures: All patients participated in telephone interviews using a series of questionnaires for evaluation of symptoms, along with a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Logistic regression models were used to evaluate risk factors for fatigue, dyspnea, symptom burden, or higher CAT scores. Results: Of 2433 patients at 1-year follow-up, 1205 (49.5%) were men and 680 (27.9%) were categorized into the severe disease group as defined by the World Health Organization guideline; the median (IQR) age was 60.0 (49.0-68.0) years. In total, 1095 patients (45.0%) reported at least 1 symptom. The most common symptoms included fatigue, sweating, chest tightness, anxiety, and myalgia. Older age (odds ratio [OR], 1.02; 95% CI, 1.01-1.02; P < .001), female sex (OR, 1.27; 95% CI, 1.06-1.52; P = .008), and severe disease during hospital stay (OR, 1.43; 95% CI, 1.18-1.74; P < .001) were associated with higher risks of fatigue. Older age (OR, 1.02; 95% CI, 1.01-1.03; P < .001) and severe disease (OR, 1.51; 95% CI, 1.14-1.99; P = .004) were associated with higher risks of having at least 3 symptoms. The median (IQR) CAT score was 2 (0-4), and a total of 161 patients (6.6%) had a CAT score of at least 10. Severe disease (OR, 1.84; 95% CI, 1.31-2.58; P < .001) and coexisting cerebrovascular diseases (OR, 1.95; 95% CI, 1.07-3.54; P = .03) were independent risk factors for CAT scores of at least 10. Conclusions and Relevance: This study found that patients with COVID-19 with severe disease during hospitalization had more postinfection symptoms and higher CAT scores.

Possible posttraumatic stress disorder in Chinese frontline healthcare workers who survived COVID-19 6 months after the COVID-19 outbreak: prevalence, correlates, and symptoms.

Suffering from COVID-19 and witnessing the suffering and deaths of patients with COVID-19 may place frontline healthcare workers (HCWs) at particularly high risk for posttraumatic stress disorder (PTSD); however, few data are available on the clinical characteristics of PTSD among frontline HCWs who survived COVID-19 ("surviving HCWs" hereafter). The present study examined the prevalence, correlates, and clinical symptoms of possible PTSD in surviving HCWs 6 months after the COVID-19 outbreak in China. A total of 291 surviving HCWs and 42 age- and gender-matched COVID-19-free frontline HCWs (control group) were recruited and administered the Chinese Essen Trauma Inventory, which was used to assess the presence of possible PTSD according to DSM-IV-TR criteria. Survivors' clinical data and characteristics of exposure to COVID-19 were collected via self-report questionnaires. Surviving HCWs had significantly higher rates of possible PTSD than controls (19.9% vs. 4.8%, P = 0.017). Correlates of PTSD in survivors were ICU admission (OR = 8.73, P = 0.003), >10 respiratory symptoms during the most symptomatic period of COVID-19 (OR = 3.08, P = 0.006), the residual symptom of dizziness (OR = 2.43, P = 0.013), the residual symptom of difficult breathing (OR = 2.23, P = 0.027), life in danger due to COVID-19 (OR = 16.59, P = 0.006), and exposure to other traumatic events (OR = 2.94, P = 0.035). Less commonly seen PTSD symptoms in survivors were having nightmares about the event (34.5%), suddenly feeling like they were living through the event suddenly (25.9%), being unable to remember an important part of the event (32.8%), and overalertness (31.0%). Nearly one-fifth of the surviving HCWs had possible PTSD 6 months after the COVID-19 outbreak. Mental health services for this vulnerable population should include periodic screening for PTSD, expanded social support, and, when necessary, psychotherapy and psychopharmacological treatment.

Bile acid-activated macrophages promote biliary epithelial cell proliferation through integrin αvß6 upregulation following liver injury.

Cholangiopathies caused by biliary epithelial cell (BEC) injury represent a leading cause of liver failure. No effective pharmacologic therapies exist, and the underlying mechanisms remain obscure. We aimed to explore the mechanisms of bile duct repair after targeted BEC injury. Injection of intermedilysin into BEC-specific human CD59 (hCD59) transgenic mice induced acute and specific BEC death, representing a model to study the early signals that drive bile duct repair. Acute BEC injury induced cholestasis followed by CCR2+ monocyte recruitment and BEC proliferation. Using microdissection and next-generation RNA-Seq, we identified 5 genes, including Mapk8ip2, Cdkn1a, Itgb6, Rgs4, and Ccl2, that were most upregulated in proliferating BECs after acute injury. Immunohistochemical analyses confirmed robust upregulation of integrin αvß6 (ITGß6) expression in this BEC injury model, after bile duct ligation, and in patients with chronic cholangiopathies. Deletion of the Itgb6 gene attenuated BEC proliferation after acute bile duct injury. Macrophage depletion or Ccr2 deficiency impaired ITGß6 expression and BEC proliferation. In vitro experiments revealed that bile acid-activated monocytes promoted BEC proliferation through ITGß6. Our data suggest that BEC injury induces cholestasis, monocyte recruitment, and induction of ITGß6, which work together to promote BEC proliferation and therefore represent potential therapeutic targets for cholangiopathies.

Characterization of an Asymptomatic Cohort of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Individuals Outside of Wuhan, China.

PURPOSE: We aimed to further clarify the epidemiological and clinical characteristics of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. METHODS: We identified close contacts of confirmed coronavirus disease 2019 (COVID-19) cases in northeast Chongqing, China, who were confirmed by real-time reverse transcription polymerase chain reaction-positive (RT-PCR+). We stratified this cohort by normal vs abnormal findings on chest computed tomography (CT) and compared the strata regarding comorbidities, demographics, laboratory findings, viral transmission and other factors. RESULTS: Between January 2020 and March 2020, we identified and hospitalized 279 RT-PCR+ contacts of COVID-19 patients. 63 (23%) remained asymptomatic until discharge; 29 had abnormal and 34 had normal chest CT findings. The mean cohort age was 39.3 years, and 87.3% had no comorbidities. Mean time to diagnosis after close contact with a COVID-19 index patient was 16.0 days, and it was 13.4 days and 18.7 days for those with abnormal and normal CT findings, respectively (P < .05). Nine patients (14.3%) transmitted the virus to others; 4 and 5 were in the abnormal and normal CT strata, respectively. The median length of time for nucleic acid to turn negative was 13 days compared with 10.4 days in those with normal chest CT scans (P < .05). CONCLUSIONS: A portion of asymptomatic individuals were capable of transmitting the virus to others. Given the frequency and potential infectiousness of asymptomatic infections, testing of traced contacts is essential. Studies of the impact of treatment of asymptomatic RT-PCR+ individuals on disease progression and transmission should be undertaken.

[Metformin: one of the possible options to reduce the mortality of severe coronavirus disease 2019?]

According to the world epidemic report, the mortality of patients with severe coronavirus disease 2019 (COVID-19) is high. Diabetic patients are more susceptible to COVID-19. Since the mortality of COVID-19 patients with diabetes is on the top of list, hyperglycemia is considered an independent risk factor for severe COVID-19. Up to now, there is few effective treatment for severe patients infected with 2019 novel coronavirus (2019-nCoV). Clinical studies observed that cytokine storms existed in patients with severe COVID-19. Sustained high levels of cytokines cause diffuse damage to pulmonary capillary endothelial cells and alveolar epithelial cells, resulting in acute respiratory distress syndrome (ARDS). ARDS is the main cause of death in COVID-19 patients. Host-directed therapy (HDT) is an emerging therapeutic method in the field of anti-infection, which can activate the self-protective immune response, suppress excessive inflammatory response, and be used to assist the treatment of traditional drugs to shorten the course of disease. Metformin has been shown to be effective in HDT and can assist in the treatment of the viral and bacterial infectious disease. This paper discusses the rationality and potential therapeutic mechanism of metformin in the treatment of severe COVID-19. It was speculated that the use of metformin for controlling blood glucose in severe COVID-19 patients with diabetes may prevent or inhibit the occurrence of ARDS, thereby reducing the mortality of COVID-19 patients. The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.