Efficacy of the neutralizing antibodies after the booster dose on SARS-CoV-2 Omicron variant and a two-year longitudinal antibody study on Wild Type convalescents.

OBJECTIVES: Waning vaccine-induced immunity and emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants which may lead to immune escape, pose a major threat to the COVID-19 pandemic. Currently, enhanced efficacy of the neutralization antibodies (NAb) produced after the booster dose of vaccinations against the Omicron variant is the main focus of vaccine strategy research. In this study we have analyzed the potency of the NAbs and IgGs produced after the third vaccine dose in patients infected with Omicron variant and wild-type (WT) SARS-CoV-2. METHODS: We enrolled 75 patients with Omicron variant breakthrough infections, and 87 patients with WT infections. We recorded the clinical characteristics and vaccination information of all patients and measured the NAb and anti-S1 (spike protein) + N (nucleocapsid protein) IgG-binding antibodies against SARS-CoV-2 in serum samples of Omicron variant-infected patients at admission, and patients with WT COVID-19 infection from the time of admission and discharge, and one-year to two-years follow-ups. RESULTS: Our results demonstrated higher NAb levels, fewer clinical symptoms, and faster viral shedding in Omicron variant infected patients vaccinated with the booster dose. Hybrid immunity (natural infection plus vaccination) induces higher NAb levels than vaccine-only immunity. NAb and IgG levels decreased significantly at one-year follow-up in WT convalescents with natural infection. The NAb and IgG levels in booster-vaccinated COVID-19 patients were higher than those in two-dose-vaccinated patients. CONCLUSION: Our results suggest that booster vaccinations are required to improve the level of protective NAbs. Moreover, our data provide important evidence for vaccination strategies based on existing vaccines.

Proteomics Investigation of Diverse Serological Patterns in COVID-19.

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.

Longitudinal observation of viral load in patients infected with Omicron variant and its relationship with clinical symptoms.

Objective: In 2022, a new coronavirus variant (Omicron) infection epidemic broke out in Shanghai, China. However, it is unclear whether the duration of this omicron variant is different from that of the prototype strain. Methods: We retrospectively analyzed 157 cases of Omicron variant infection in Taizhou Public Health Center from March 29, 2022, to April 18, 2022, and observed the dynamics of nucleic acid Ct values during the admission and discharge of patients. Clinical and laboratory indicators of these patients were also obtained. Results: Compared to the prototype strain, the Omicron variant showed a broad population susceptibility in infected individuals (regardless of age and presence of underlying disease) and had slight damage to the immune system and renal function; the viral loads peaked was 2-3 days from disease onset; the median duration of omicron variant was 15-18 days; the nucleic acid Ct value of nasopharyngeal swabs of infected patients is lower than that of throat swabs, and the Ct value of oropharyngeal swabs is unstable during the recovery period. Conclusion: Therefore, we found that the time to peak viral load of this Omicron variant was 2-3 days after the onset of the disease, and the duration was 15-18 days; symptomatic patients had higher viral load and longer hospitalization time. This finding will provide a basis for understanding omicron variants and formulating the national prevention and control strategy.

Physical condition, psychological status, and posttraumatic stress disorder among recovered COVID-19 subjects: A mediation analysis.

The physical condition of individuals who contracted COVID-19 had a profound influence on mitigating the physical and psychological impact of the disease and the symptoms of posttraumatic stress disorder (PTSD). Little attention has been focused on the influence of physical condition on PTSD among recovered COVID-19 subjects. This study explored the relationship between physical and psychological status and PTSD and the potential mechanisms. Questionnaires were completed by 73 (50.7%, 73/144) COVID-19 recovered subjects who were diagnosed in Taizhou, Zhejiang, China. We conducted a face-to-face survey from January 17 to March 10, 2020. The mediation analysis approach was applied in this research. Our data show that recovered COVID-19 subjects who were in better physical condition exhibited fewer psychological problems [B (95%CI), (-1.65 -3.04, -0.26)] and lower PTSD [B (95%CI), -6.13 (-9.43, -2.83)]. In addition, the worse the psychological status of recovered COVID-19 subjects was, the stronger the PTSD (B [95%CI], 0.58 [0.02, 1.14]). Moreover, psychological status could significantly mediate the impact of physical condition on PTSD (ß1θ2 = -0.87). Together, COVID-19 recovered subjects who have better physical condition could decrease their PTSD, and the worse the physical condition of COVID-19 recovered subjects would increase their psychological problems. Our finding about psychological status could significantly mediate the impact of the physical condition on PTSD might be useful for medical institutions and the government seeking to help with the follow-up rehabilitation training of recovered COVID-19 subjects.

Longitudinal observation of viral load in patients infected with Omicron variant and its relationship with clinical symptoms

Objective In 2022, a new coronavirus variant (Omicron) infection epidemic broke out in Shanghai, China. However, it is unclear whether the duration of this omicron variant is different from that of the prototype strain. Methods We retrospectively analyzed 157 cases of Omicron variant infection in Taizhou Public Health Center from March 29, 2022, to April 18, 2022, and observed the dynamics of nucleic acid Ct values during the admission and discharge of patients. Clinical and laboratory indicators of these patients were also obtained. Results Compared to the prototype strain, the Omicron variant showed a broad population susceptibility in infected individuals (regardless of age and presence of underlying disease) and had slight damage to the immune system and renal function;the viral loads peaked was 2-3 days from disease onset;the median duration of omicron variant was 15-18 days;the nucleic acid Ct value of nasopharyngeal swabs of infected patients is lower than that of throat swabs, and the Ct value of oropharyngeal swabs is unstable during the recovery period. Conclusion Therefore, we found that the time to peak viral load of this Omicron variant was 2-3 days after the onset of the disease, and the duration was 15-18 days;symptomatic patients had higher viral load and longer hospitalization time. This finding will provide a basis for understanding omicron variants and formulating the national prevention and control strategy.

Physical condition, psychological status, and posttraumatic stress disorder among recovered COVID-19 subjects: A mediation analysis

The physical condition of individuals who contracted COVID-19 had a profound influence on mitigating the physical and psychological impact of the disease and the symptoms of posttraumatic stress disorder (PTSD). Little attention has been focused on the influence of physical condition on PTSD among recovered COVID-19 subjects. This study explored the relationship between physical and psychological status and PTSD and the potential mechanisms. Questionnaires were completed by 73 (50.7%, 73/144) COVID-19 recovered subjects who were diagnosed in Taizhou, Zhejiang, China. We conducted a face-to-face survey from January 17 to March 10, 2020. The mediation analysis approach was applied in this research. Our data show that recovered COVID-19 subjects who were in better physical condition exhibited fewer psychological problems [B (95%CI), (−1.65 −3.04, −0.26)] and lower PTSD [B (95%CI), −6.13 (−9.43, −2.83)]. In addition, the worse the psychological status of recovered COVID-19 subjects was, the stronger the PTSD (B [95%CI], 0.58 [0.02, 1.14]). Moreover, psychological status could significantly mediate the impact of physical condition on PTSD (β1θ2 = −0.87). Together, COVID-19 recovered subjects who have better physical condition could decrease their PTSD, and the worse the physical condition of COVID-19 recovered subjects would increase their psychological problems. Our finding about psychological status could significantly mediate the impact of the physical condition on PTSD might be useful for medical institutions and the government seeking to help with the follow-up rehabilitation training of recovered COVID-19 subjects.

Differences Between Omicron Infections and Fever Outpatients: Comparison of Clinical Manifestations and Initial Routine Hematology Indicators.

Purpose: We evaluated the differences between patients with SARS-CoV-2 Omicron variant infections and Fever outpatients, so that prevention and control measures can be taken in time. Patients and Methods: This study retrospectively analyzed 65 patients with SARS-CoV-2 Omicron variant. Sixty-nine age- and sex-matched Fever outpatients were enrolled during the same period of time. We also reanalyzed data from 81 SARS-CoV-2 Wild-Type-infected patients. We compared the clinical characteristics and initial indexes of routine tests among the 3 groups. Results: A total of 93.8% of the patients with Omicron infections had clinical symptoms, and the major symptoms were cough, fever and pharyngalgia. Pharyngalgia was a specific manifestation in Omicron group compared to Wild-Type group. The white blood cell of the Omicron group was lower than that of the Fever group [5.0 (3.6-6.1) vs 10.1 (7.6-12.9) ×109/L, P < 0.001]. The neutrophil count in Omicron group was lower than that in Fever and Wild-Type group [2.6 (1.8-3.9) vs 8.1 (5.9-10.9), P < 0.001; 2.6 (1.8-3.9) vs 3.4 (2.5-4.7) ×109/L, P < 0.001]. The white blood cell and neutrophil counts were lower in Omicron group than in the Fever group. The top 5 major symptoms were fever, cough, pharyngalgia, headache and expectoration. Conclusion: There are differences between the patients with Omicron infections and Fever outpatients, both in clinical manifestations and initial routine hematology indicators. We hope to provide some clues for early identification combined with a history of living in the epidemic area.

Clinical practice of rapid antigen tests for SARS-CoV-2 Omicron variant: A single-center study in China.

Responding to the fast-spreading SARS-CoV-2 Omicron variant, to improve screening efficiency, rapid antigen tests (RATs) were first added as a supplementary detection method in China in mid-March, 2022. What and how big a role RATs should play need to be supported by clinical data. Here, RAT performance and relevant factors in comparison with nucleic acid amplification tests (NAATs) were assessed in Omicron-infected inpatients. From the NAAT results, nasopharyngeal swabs (NPs) performed better than oropharyngeal swabs (OPs). RATs tested on NAAT positive NPs performed better than those with OP-positive samples. The RAT positivity rate was strongly associated with high levels of N and OFR1ab genes, especially in NPs where patients also had significantly longer hospital stays and shorter days from symptom onset to RAT testing. Self-performed RATs had a detection accuracy that was comparable to professionally performed RATs when the subjects were well guided. The antigen negative rate of the studied patients was 100% at discharge. These findings suggest that, in addition to a supplementary detection role, RATs can be an important strategy for evaluating the disease progression of Omicron-infected inpatients. This study provides important clinical data to support better rules regarding RATs under China's COVID-19 prevention and control policy.

The Correlation Between Triglyceride-Glucose Index and SARS-CoV-2 RNA Re-Positive in Discharged COVID-19 Patients.

Objective: Facing the challenge to manage the SARS-CoV-2 RNA re-positive in discharged COVID-19 patients, it is necessary to explore the limited early risk factors for identifying SARS-CoV-2 RNA re-positive. The triglyceride and glucose index (TyG) has been developed as a surrogate marker of insulin resistance. This study aims to evaluate the correlation of the TyG index with the re-positive of COVID-19. Methods: A total of 144 COVID-19 patients from Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (China) were enrolled in this study. All of them were discharged after recovery according to the guidelines. We compared the clinical characteristics and laboratory indexes of re-positive and non-re-positive COVID-19 patients, and analyzed the early risk factors for identifying SARS-CoV-2 RNA re-positive. Results: During the follow-up, a total of 18 patients were tested re-positive for SARS-CoV-2 RNA. Re-positive COVID-19 patients had higher proportion of abidol (P=0.018), antibiotic use (P=0.024) and hepatitis-based diseases (P=0.042), and higher heart rate (P=0.011) at admission (P=0.026), while lower TyG index (P=0.036), eGFR (P=0.034), TG (P=0.015) and C1q (P=0.023). Multivariate logistic regression analysis showed that TyG index was an independent risk factor for the re-positive of SARS-CoV-2 RNA (P=0.005). TyG index was significantly correlated with Glu (P<0.001), TG (P<0.001) and HDL-C (P<0.001). In addition, it was found that TyG index decreased at SARS-CoV-2 RNA positive stage and increased at negative stage (P<0.05). Conclusion: TyG index may be a valuable marker for identifying the re-positive of COVID-19 patients and may play a role in determining the stage of the patient's disease. We hope to provide a reliable theoretical basis for clinical prediction and effective control of re-positive episodes, and to provide a breakthrough for further research on the causes of re-positive episodes and the immune mechanism of the virus.

Quality of Life and Mental Health Status in Recovered COVID-19 Subjects at Two Years after Infection in Taizhou, China: A Longitudinal Cohort Study.

According to previous studies, mental status in 1-year COVID-19 survivors might range from 6-43%. Longer-term psychological consequences in recovered COVID-19 subjects are unknown, so we analyzed longer-term quality of life and mental status in recovered COVID-19 subjects at 2 years after infection. Among 144 recovered COVID-19 subjects in the Taizhou region, 73 and 45 completed face-to-face follow-ups at the first year and second year after infection, respectively, with a 61.7% follow-up rate. The questionnaire, which was administered at both follow-ups, included questions about quality of life, psychological health, and post-traumatic stress disorder (PTSD). The Mann-Whitney U test was used to the differences of each scale between the first and second year. Among the 45 people who completed both follow-up visits, the incidence of psychological problems was 4.4% (2/45) in the first year, and no new psychological abnormalities were observed in the second year. Quality of life improved, while the General Health Questionnaire (GHQ-12) and Impact of Event Scale-Revised (IES-R) scores did not improve over time. The incidence of mental disorders was lower than those in previous studies. Multidisciplinary management for COVID-19 in this study hospital may have reduced the frequency to a certain extent. However, among those with mental health problems, such problems may exist for a long time, and long-term attention should be given to the psychological status of recovered COVID-19 subjects.

Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19.

The utility of the urinary proteome in infectious diseases remains unclear. Here, we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine, but only 124 in serum using TMT-based proteomics. The decrease in urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. The downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomics analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomics analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.

Potential Use of Serum Proteomics for Monitoring COVID-19 Progression to Complement RT-PCR Detection.

RT-PCR is the primary method to diagnose COVID-19 and is also used to monitor the disease course. This approach, however, suffers from false negatives due to RNA instability and poses a high risk to medical practitioners. Here, we investigated the potential of using serum proteomics to predict viral nucleic acid positivity during COVID-19. We analyzed the proteome of 275 inactivated serum samples from 54 out of 144 COVID-19 patients and shortlisted 42 regulated proteins in the severe group and 12 in the non-severe group. Using these regulated proteins and several key clinical indexes, including days after symptoms onset, platelet counts, and magnesium, we developed two machine learning models to predict nucleic acid positivity, with an AUC of 0.94 in severe cases and 0.89 in non-severe cases, respectively. Our data suggest the potential of using a serum protein-based machine learning model to monitor COVID-19 progression, thus complementing swab RT-PCR tests. More efforts are required to promote this approach into clinical practice since mass spectrometry-based protein measurement is not currently widely accessible in clinic.

Laboratory indicators in COVID-19 and other pneumonias: Analysis for differential diagnosis and comparison of dynamic changes during 400-day follow-up.

BACKGROUND: COVID-19 is spreading rapidly all over the world, the patients' symptoms can be easily confused with other pneumonia types. Therefore, it is valuable to seek a laboratory differential diagnostic protocol of COVID-19 and other pneumonia types on admission, and to compare the dynamic changes in laboratory indicators during follow-up. METHODS: A total of 143 COVID-19, 143 bacterial pneumonia and 145 conventional viral pneumonia patients were included. The model group consisted of 140 COVID-19, 80 bacterial pneumonia and 60 conventional viral pneumonia patients, who were age and sex matched. We established a differential diagnostic model based on the laboratory results of the model group on admission via a nomogram, which was validated in an external validation group. We also compared the 400-day dynamic changes of the laboratory indicators among groups. RESULTS: LASSO regression and multivariate logistic regression showed that eosinophils (Eos), total protein (TP), prealbumin (PA), potassium (K), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) could differentiate COVID-19 from other pneumonia types. The C-index of the nomogram model was 0.922. Applying the nomogram to the external validation group showed an area under the curve (AUC) of 0.902. The 400-day change trends of the laboratory indexes varied among subgroups divided by sex, age, oxygenation index (OI), and pathogen. CONCLUSION: The laboratory model was highly accurate at providing a new method to identify COVID-19 in pneumonia patients. The 400-day dynamic changes in laboratory indicators revealed that the recovery time of COVID-19 patients was not longer than that of other pneumonia types.

Clinical evaluation of a rapid colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG.

BACKGROUND: Since December 2019, there had been an outbreak of COVID-19 in Wuhan, China. At present, diagnosis COVID-19 were based on real-time RT-PCR, which have to be performed in biosafe laboratory and is unsatisfactory for suspect case screening. Therefore, there is an urgent need for rapid diagnostic test for COVID-19. OBJECTIVE: To evaluate the diagnostic performance and clinical utility of the colloidal gold immunochromatography assay for SARS-Cov-2 specific IgM/IgG anti-body detection in suspected COVID-19 cases. METHODS: In the prospective cohort, 150 patients with fever or respiratory symptoms were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang province, China, between January 20 to February 2, 2020. All patients were tested by the colloidal gold immunochromatography assay for COVID-19. At least two samples of each patient were collected for RT-PCR assay analysis, and the PCR results were performed as the reference standard of diagnosis. Meanwhile 26 heathy blood donor were recruited. The sensitivity and specificity of the immunochromatography assay test were evaluated. Subgroup analysis were performed with respect to age, sex, period from symptom onset and clinical severity. RESULTS: The immunochromatography assay test had 69 positive result in the 97 PCR-positive cases, achieving sensitivity 71.1% [95% CI 0.609-0.797], and had 2 positive result in the 53 PCR-negative cases, achieving specificity 96.2% [95% CI 0.859-0.993]. In 26 healthy donor blood samples, the immunochromatography assay had 0 positive result. In subgroup analysis, the sensitivity was significantly higher in patients with symptoms more than 14 days 95.2% [95% CI 0.741-0.998] and patients with severe clinical condition 86.0% [95% CI 0.640-0.970]. CONCLUSIONS: The colloidal gold immunochromatography assay for SARS-Cov-2 specific IgM/IgG anti-body had 71.1% sensitivity and 96.2% specificity in this population, showing the potential for a useful rapid diagnosis test for COVID-19. Further investigations should be done to evaluate this assay in variety of clinical settings and populations.

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study.

Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.