To complement serology as a tool in public health interventions, we introduced the "celluloepidemiology" paradigm where we leveraged pathogen-specific T cell responses at a population level to advance our epidemiological understanding of infectious diseases, using SARS-CoV-2 as a model. Applying flow cytometry and machine learning on data from more than 500 individuals, we showed that the number of T cells with positive expression of functional markers not only could distinguish patients who recovered from COVID-19 from controls and pre-COVID donors but also identify previously unrecognized asymptomatic patients from mild, moderate, and severe recovered patients. The celluloepidemiology approach was uniquely capable to differentiate health care worker groups with different SARS-CoV-2 exposures from each other. T cell receptor (TCR) profiling strengthened our analysis by revealing that SARS-CoV-2-specific TCRs were more abundant in patients than in controls. We believe that adding data on T cell reactivity will complement serology and augment the value of infection morbidity modeling for populations.

We described waning in anti-SARS-CoV-2 IgG in adult general populations infected during the first wave of the COVID-19 pandemic in 2020 across three European countries.

Coordinated analyses were conducted separately in three population-based cohorts with complementary follow-up schedules: the KoCo19 (Germany), EpiCov (France), and CON-VINCE (Luxembourg) cohorts. Serological follow-up was based on the anti-SARS-CoV-2 ELISA-S IgG (Euroimmun) assay. We selected all adults aged 18-79 who had a positive serology (IgG optical density (OD) ratio ≥1.1) between February and July 2020, and at least one subsequent IgG measurement within the following 12 months, while still non-vaccinated.

The proportion of seroreversion was 0% within the four first months, based on Koco19 data (n = 65 participants). In the longer term, 31.3% of participants had seroreverted at 6 months (95%CI: 24.4-39.1) (based on EpiCov data, n = 599), 31.3% (95%CI: 11.0-58.7) at 12 months (based on CON-VINCE data, n = 16). From EpiCov data, both baseline low IgG levels and seroneutralization negativity remained predictive of seroreversion in multivariable analysis.

From population-based cohorts, anti-S IgG levels remained stable during the first 4 months following SARS-CoV-2 infection. Most of the decay occurred afterward; nearly one-third of people seroreverted 6 and 12 months later. Low IgG levels and seroneutralization negativity were independent predictors of seroreversion.

The effectiveness of multiple COVID-19 vaccinations in individuals with a history of SARS-CoV-2 infection remains unclear; specifically, elucidation of the durability of anti-viral antibody responses could provide important insights for epidemiological applications. We utilized the BU ELISA protocol to measure the circulating SARS-CoV-2 receptor-binding domain (RBD) and nucleocapsid (N) specific IgG and IgA antibody levels in a cohort of individuals infected with SARS-CoV-2 in the spring of 2020, with the sample collection spanning six months to two years post-symptom onset. Further, we interrogated the neutralization activity of these samples against the ancestral SARS-CoV-2 (WA-1) and Delta and Omicron (BA.1) variants. Consistent with previous studies, we found a more rapid waning of anti-N compared to anti-RBD antibodies in months prior to the first vaccinations. Vaccine-induced antibody responses in individuals previously infected with SARS-CoV-2 were elevated and sustained for more than one year post-vaccination. Similarly, neutralization activity against WA-1, Delta, and Omicron increased and remained higher than pre-vaccination levels for one year after the first COVID-19 vaccine dose. Collectively, these results indicate that infection followed by vaccination yields robust antibody responses against SARS-CoV-2 that endure for one year. These results suggest that an annual booster would stably boost anti-SARS-CoV-2 antibody responses, preventing infection and disease.

We report Singapore's convalescent plasma (CP) programme during the first year of the COVID-19 pandemic. Based on historical data and its potential therapeutic promise, CP was offered as an experimental treatment option for severe or high-risk COVID-19 patients when established therapeutics were lacking.

The CP programme was implemented under monitored expanded access approved by Singapore's Ministry of Health. CP donors were primarily selected based on specific antibody titres, while suitable recipients were chosen based on risk factors and disease severity. Operational protocols and logistical considerations are discussed in-depth.

Between April 2020 and September 2020, the CP donor programme successfully collected 33 plasma units from 27 qualified donors. Seven patients received CP treatment under this programme. Six of the seven recipients of CP survived for more than 28 days post-transfusion and were discharged alive. Given the availability of other validated therapeutic options, the CP programme was officially suspended in September 2021.

This study provides a comprehensive overview of the intricacies of Singapore's CP programme, from its operational challenges to the observed clinical outcomes, while highlighting the potential benefits and complexities of CP as a therapeutic option. Successful implementation of the CP programme requires robust collaboration across multidisciplinary teams. Access to serological tests was crucial for donor selection. Both the selection of CP with high neutralising antibodies and careful selection of appropriate recipients are key aspects to optimise the therapeutic success of CP. A meticulous approach is warranted if CP were to be used in future pandemics.

This review provides a broad overview of lessons learned in the five years since COVID-19 was identified. It is a bimodal disease, starting with an initially virus-driven phase, followed by resolution or ensuing inappropriate immune activation causing severe inflammation that is no longer strictly virus dependent. Humoral immunity is beneficial for preventing or attenuating the early stage, without benefit once the later stage begins. Neutralizing antibodies elicited by natural infection or vaccination are short-lived and highly vulnerable to viral sequence variation. By contrast, cellular immunity, particularly the CD8+ T cell arm, has a role in preventing or attenuating severe disease, is far less susceptible to viral variation, and is longer-lived than antibodies. Finally, an ill-defined phenomenon of prolonged symptoms after acute infection, termed "long COVID," is poorly understood but may involve various immunologic defects that are hyperactivating or immunosuppressive. Remaining issues include needing to better understand the immune dysregulation of severe disease to allow more tailored therapeutic interventions, developing antibody strategies that cope with the viral spike sequence variability, prolonging vaccine efficacy, and unraveling the mechanisms of long COVID to design therapeutic approaches.

The antibody-mediated immune response is crucial for the development of protective immunity against SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Understanding the interaction between SARS-CoV-2 and the immune system is critical because new variants emerge as a result of the virus's ongoing evolution. Understanding the function of B cells in the SARS-CoV-2 infection process is critical for developing effective and long-lasting vaccines against this virus. Triggered by the innate immune response, B cells transform into memory B cells (MBCs). It is fascinating to observe how MBCs provide enduring immune defence, not only eradicating the infection but also safeguarding against future reinfection. If there is a lack of B cell activation or if the B cells are not functioning properly, it can lead to a serious manifestation of the disease and make immunisation less effective. Individuals with disruptions in the B cells have shown increased production of cytokines and chemokines, resulting in a poor prognosis for the disease. Therefore, we have developed an updated review article to gain insight into the involvement of B cells in SARS-CoV-2 infection. The discussion has covered the generation, functioning, and dynamics of neutralising antibodies (nAbs). Furthermore, we have emphasised immunotherapeutics that rely on nAbs.

A major challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been assessing the intensity, dynamics, and determinants of the antibody responses after infection and/or vaccination. Therefore, we aimed to characterize the longitudinal dynamics of the antibody responses among naturally infected individuals and individuals who achieved hybrid immunity in a large Canadian cohort. We demonstrate that anti-Spike IgGs and neutralizing antibody dynamics vary greatly among individuals with COVID-19, in peak antibody levels, rate of waning, and longevity of the antibody response. Additionally, we found an association between robust antibody responses and individuals with severe COVID-19 clinical symptoms during the first-month post-symptom onset. For individuals who achieved hybrid immunity, a robust increase in anti-S1 IgGs and neutralizing antibodies followed the first vaccination dose; however, there was a minimal increase in the anti-S1 IgGs and neutralizing antibody titers after administration of the second dose of the vaccine. Furthermore, neutralizing antibodies elicited by the wild-type virus alone were largely ineffective against emerging variants of concern in our natural infection-only cohort, in contrast to a much broader and more robust neutralization profile observed in individuals who achieved hybrid immunity. Our findings emphasize the need for global SARS-CoV-2 vaccination efforts to further sustain protective immune responses required to minimize viral spread and disease severity in the population. As SARS-CoV-2 variants continue to emerge, understanding the interplay between previous infections, vaccine durability, and virus evolution will be critical for guiding ongoing vaccination strategies.

A major challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been assessing the intensity, dynamics, and determinants of the antibody response after infection and/or vaccination. Our paper addresses this in a large Canadian cohort with antibody responses that were generated by natural infection as well as vaccine in some persons studied.

To track the level of serum antibodies in Fuzhou residents and analyze the possible influencing factors of serum antibodies, so as to provide a scientific basis for the adjustment of population immunity and prevention and control strategies.

Residents in the Fuzhou community who had symptoms of covid-19 infection or who had tested positive for nucleic acid or antigen since December 2022 were selected for the questionnaire survey and their sera were collected to analyze the trend of antibody changes, the antibody level was divided into high antibody group and low antibody group according to the literature data. The possible influencing factors of serum antibody level was analyzed by multivariate logistic regression model.

A total of 2,521 Fuzhou residents were adopted in the study, including 223 in the high antibody group and 194 in the low antibody group. A univariate analysis showed that, there were significant differences in age (Z=-4.028, P<0.00), occupation (χ2 = 18.591, P=0.005), typical symptoms after the first infection (χ2 = 9.784, P=0.002), history of surgery (χ2 = 29.542, P<0.001), symptoms lasting more than 2 weeks after the first infection (χ2 = 4.887, P=0.027), smoking (χ2 = 18.524, P<0.001) and drinking (χ2 = 19.578, P<0.001) between the high antibody group and the low antibody group. Multivariate regression models show that, age (OR= 1.011, 95%CI: 1.002~1.020, P=0.017), history of surgery (OR=4.956,95%CI: 2.606~9.423, P<0.001),smoking (OR=2.089, 95%CI: 1.002~4.355, P=0.049), drinking (OR=2.214, 95%CI: 1.066~4.600, P=0.033) were the risk factors affecting antibody level. Typical symptoms after the first infection (OR=0.224, 95%CI: 0.086~0.579, P=0.002) and symptoms lasting more than 2 weeks after the first infection (OR=0.432, 95%CI: 0.258~0.723, P=0.001) were protective factors. By observing the trend of antibody changes in 3, 6 and 9 months, we found that the level of IgG antibody showed a decreasing trend.

The high level of protection was more likely to occur in young adults, people without operation history, people without smoking history, people without drinking history, people with typical symptoms after the first infection and symptoms lasting more than 2 weeks after the first infection. The level of IgG antibody was decreased in general, so it is necessary to strengthen immunization.

To study the safety of resuming antitumor therapy in tumor patients infected with COVID-19.

We collected the clinical information of patients with tumors who were infected with COVID-19 and resume antitumor therapy between December 2022 and June 2023. Information about antitumor therapy, COVID-19-related symptoms, laboratory tests, antitumor therapy-related adverse events (AEs), and re-infection with COVID-19 were recorded. Primary endpoints included the incidence of AEs and re-infection of COVID-19. The secondary endpoints included the incidence and duration of COVID-19 related symptoms.

The most common COVID-19 symptoms were fever (39.5%), cough (37.2%), and fatigue (44.2%). Most patients' symptoms lasted no more than a week Two patients were re-infected with COVID-19. All-grade AEs with an incidence rate > 10% included anemia, increased gamma-glutamyl transferase (GGT), anorexia, neutropenia, hypocalcemia, leukopenia, thrombocytopenia, increased alanine aminotransferase, increased aspartate aminotransferase, hypokalemia, hyponatremia, and nausea. Grade 3-4 AEs with an incidence rate higher than 5% included anemia, neutropenia, leukopenia, thrombocytopenia, anorexia, and vomiting. The incidence of AEs before and after COVID-19 infection did not show a significant difference.

Resuming antitumor therapy early after SARS-CoV-2 test turned negative did not increase antitumor therapy-related AEs or the incidence of re-infection in COVID-19 infection patients.

Cancer patients are considered to have a higher risk of developing severe Coronavirus Disease 2019 (COVID-19) and a higher mortality rate. Moreover, poor prognosis observed in them is associated with multiple co-morbidities. Ayurveda can prove to be effective in preventing COVID-19 as well as improving clinical outcomes against COVID-19 in cancer patients.

To evaluate the effect of Ayurvedic treatments given to cancer patients as also a preventive modality against COVID-19 infections.

700 cancer patients were enrolled in the study. The demographic information regarding their age, sex, organs involved, stage, pre-existing comorbidities, Karnofsky score, addictions, undergoing conventional cancer treatment, type of conventional treatment, and duration of Ayurvedic cancer treatment was collected from the institutional records. These patients were interviewed telephonically or in person to obtain information related to their COVID-19 status from March 2020 to Sep 2021, which included a) whether they were affected with COVID-19 or not, b) If affected, the severity of COVID-19 symptoms, c) vaccination status, d) mortality, and e) if in contact with relative affected by COVID-19.

The surveyed cohort had 56 years as the median age, more female patients, Karnofsky score between 80 and 100, and hypertension as well as diabetes as major co-morbidities. During the 1st and 2nd waves, 34 (4.85%) and 65 patients (10.09 %) were COVID-19 positive while 4.91 % and 11.11% of patients with addictions were covid positive, respectively, the rest remained unaffected. There was no specific trend in % of COVID-19-positive cancer patients concerning stage, but those with stage IV undergoing conventional treatment showed increased prevalence (p < 0.001). Prolonged Ayurvedic treatment exhibited a decreasing trend in % COVID-19 positive patients, which is highly significant (p < 0.001). Specifically, those undergoing conventional therapy, and also received Ayurvedic treatment simultaneously for more than 3 years remained unaffected by COVID-19, which was statistically significant in both waves (p < 0.001).

Ayurvedic treatments given to cancer patients are effective in preventing COVID-19 infections in these patients.

Despite advances in metabolomic research on COVID-19, existing studies have small sample sizes and few have comprehensively described the metabolic characteristics of patients with COVID-19 at each stage. In this systematic review, we aimed to summarise the similarities and differences of biomarkers in patients with COVID-19 of different severity and describe their metabolic characteristics at different stages.

We retrieved studies from PubMed, Embase, Web of Science, and the Cochrane Library published by October 2022. We performed a meta-analysis on untargeted and targeted metabolomics research data, using the ratio of means as the effect size. We compared changes in metabolite levels between patients with varying severity and controls and investigated sources of heterogeneity through subgroup analyses and meta-regression analysis.

We included 22 cohorts from 21 studies, comprising 2421 participants, including COVID-19 patients of varying severity and healthy controls. We conducted meta-analysis and heterogeneity analysis on the 1058 metabolites included in the study. The results indicated that, compared to the healthy control group, 23 biomarkers were associated with mild cases (P < 0.05), 3 biomarkers with moderate cases (P < 0.05), and 37 biomarkers with severe cases (P < 0.05). Pathway enrichment analysis revealed significant disturbances in amino acid metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, pantothenate and CoA biosynthesis, the tricarboxylic acid cycle, taurine and hypotaurine metabolism, and nitrogen metabolism in patients with mild, moderate, and severe disease. Additionally, we found that each severity stage exhibited unique metabolic patterns (all P < 0.05) and that the degree of metabolic dysregulation progressively worsened with increasing disease severity (P < 0.05).

The results of our meta-analysis indicate the similarities and differences of biomarkers and metabolic characteristics of patients with different severity in COVID-19, thereby providing new pathways for the study of pathogenesis, the development precise treatment, and the formulation of comprehensive strategies.

PROSPERO: CRD42022369937.

The SARS-CoV-2 Omicron variant and its sublineages continue to circulate widely. Clinical outcomes with this variant differ among individuals, primarily influenced by host immunity. Previous studies have explored the relationship between immune responses and severe diseases in infected or convalescent patients. However, the impact of vaccine-induced immune responses on disease severity, especially in cases of mild infection following breakthrough infection, remains unclear. This is primarily due to the lack of assessment of immune status in vaccinated individuals before infection. In this study, we aimed to elucidate the causality between virus-specific cellular and humoral immune responses and the severity of symptoms in breakthrough infected patients from a long-term follow-up post-vaccination cohort. A questionnaire survey was conducted to collect general symptoms upon breakthrough infection with the Omicron variants. Plasma levels of specific antibodies (neutralizing antibodies, anti-S IgG, and anti-N IgG) and T cell responses induced by inactivated SARS-CoV-2 vaccine were evaluated. The findings revealed that individuals with milder symptoms, particularly lower peak fever temperatures, exhibited higher antibody levels and enhanced T cell activation and responses prior to infection. This suggests that cellular and humoral immunity induced by inactivated vaccines may provide protection against severe clinical symptoms following breakthrough infection.

Repeated vaccinations and infections have led to diverse states of hybrid immunity against SARS-CoV-2 in the global population. However, age and comorbidities can compromise protection against severe disease, and antibody-mediated immunity is undercut by viral immune escape mutations. Whether and to what extent durable T cell responses compensate for reduced humoral immunity, particularly in the elderly, have not been investigated. Here, we utilize SARS-CoV-2-specific and pan-coronavirus-derived peptide pools, including or excluding spike glycoprotein-derived epitopes, to measure vaccination and infection induced pan-human endemic coronavirus (PHEC)-directed T cell immunity. In contrast to vaccinated individuals, hybrid immunity induced by vaccination and SARS-CoV-2 infection comprises high frequencies of PHEC-reactive T cells with comparable frequencies and functional TCR avidities across all age groups. With waning humoral immunity and vulnerability to escape mutations, PHEC-reactive T cells may provide critical protection. Our findings underscore the importance of incorporating pan-coronavirus T cell epitopes in future vaccine strategies.

Background/Objectives: The SARS-CoV-2's high mutations and replication rates contribute to its high infectivity and resistance to current vaccinations and treatments. The primary cause of resistance to most current treatments aligns within the coding regions for the spike S protein of SARS-CoV-2 that has mutated. As a potential novel immunotherapy, we generated a novel fusion protein composed of a soluble ACE2 (sACE2) linked to llama-derived anti-CD16 that targets different variants of spike proteins and enhances natural killer cells to target infected cells. Methods: Here, we generated a novel sACE2-AntiCD16VHH fusion protein using a Gly4Ser linker, synthesized and cloned into the pLVX-EF1alpha-IRES-Puro vector, and further expressed in ExpiCHO-S cells and purified using Ni+NTA chromatography. Results: The fusion protein significantly blocked SARS-CoV-2 alpha, beta, delta, gamma, and omicron S-proteins binding and activating angiotensin-converting enzyme receptor-2 (ACE2) on ACE2-expressing RAW-Blue macrophage cells and the secretion of several key inflammatory cytokines, G-CSF, MIP-1A, and MCP-1, implicated in the cytokine release storm (CRS). The sACE2-Anti-CD16VHH fusion protein also bridged NK cells to ACE2-expressing human lung carcinoma A549 cells and significantly activated NK-dependent cytotoxicity. Conclusions: The findings show that a VHH directed against CD16 could be an excellent candidate to be linked to soluble ACE2 to generate a bi-specific molecule (sACE2-AntiCD16VHH) suitable for bridging effector cells and infected target cells to inhibit SARS-CoV-2 variant spike proteins binding to the ACE2 receptor in the RAW-Blue cell line and pro-inflammatory cytokines and to activate natural killer cell cytotoxicity.

The existing literature has described the common symptoms and long-term effects of coronavirus disease (COVID-19). However, there is a lack of detailed information on how different degrees of disease severity affect survivors differently. This study aims to fill that gap by evaluating the symptoms, physical activity, and functionality of COVID-19 survivors across a spectrum of severity levels, comparing them with those of healthy individuals.

An observational study was carried out following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria and checklist. Participants were divided into 5 groups based on COVID-19 severity according to the World Health Organization classification: healthy (COVID-19-negative), mild (symptomatic without pneumonia or dyspnoea), moderate (pneumonia and dyspnoea without hospitalisation), severe (severe pneumonia requiring hospitalisation), and critical (severe pneumonia with admission to the intensive care unit). Descriptive variables, symptoms (Fatigue Borg Scale, Fatigue Impact Scale, Fatigue Severity Scale, Dyspnoea Borg Scale, Visual Analogue Scale, Hospital Anxiety and Depression Scale, and European Quality of Life-5 Dimensions), physical activity (the International Physical Activity Questionnaire) and functionality (Patient-Specific Functional Scale, Short Physical Performance Battery, Arm Curl test, and 2 min step test) were measured.

A total of 304 participants were included: healthy (n = 42), mild (n = 143), moderate (n = 49), severe (n = 52), and critical (n = 18) COVID-19 patients. The impact of COVID-19 on surviving patients varies significantly with the severity of the disease. The results show that the hospitalisation time, age, and comorbidities of the patients are greater in those with a greater severity of the disease. Patients with more severe COVID-19 also experience greater frailty, dysphagia, fatigue, dyspnoea, and pain. Additionally, those with severe cases have poorer overall health, reduced physical activity, and diminished functionality. No evidence of post-COVID-19 anxiety or depression is found in the sample, even considering the timeframe between the negative test and the assessment.

Patients with higher COVID-19 severity (severe or critical) experience more symptoms than those with lower COVID-19 severity (mild or moderate). Additionally, those with severe cases have poorer overall health, reduced physical activity and diminished functionality. Register: Clinicaltrials.gov: NCT05731817.

Owing to their ability to reliably detect even very rare antigen-specific B cells in cellular isolates such as peripheral blood mononuclear cells (PBMC), and doing so robustly in a high throughput-compatible manner, B cell ELISPOT/FluoroSpot (collectively "B cell ImmunoSpot") tests have become increasingly attractive for immune monitoring in regulated settings. Presently, there are no guidelines for the qualification and validation of B cell ImmunoSpot assay results. Here, we propose such guidelines, building on the experience acquired from T cell ImmunoSpot testing in an environment adhering to the requirements of regulatory bodies yet taking the unique features of B cell assays into account. A streamlined protocol is proposed that permits the performance of all tests needed for the formal validation of an antigen-specific B cell ImmunoSpot assay in only three experiments, utilizing 2.2 × 107 PBMC per donor. Subsequently, utilizing only 1-2 × 106 PBMC per sample (obtainable from 1 to 2 mL of blood), a validated multiplexed assay enables accurate quantification of the frequency of antigen-specific memory B cell-derived blasts secreting IgM, IgG, IgA or IgE antibodies. Collectively, such multiplexed B cell ImmunoSpot assays offer immense value for B cell immune monitoring programs due to their ease of implementation, scalability, applicability to essentially any antigenic system, economy of PBMC utilization, and last but not least, the high content information gained.

A descriptive study was carried out with health professionals in Sao Paulo city. Were included individuals vaccinated with 2 doses of the inactivated vaccine. Demographic, clinical and vaccination information was obtained from professionals with or without comorbidities. Two serological assays were used to identify the presence and quantity of anti-Spike IgG in serum samples. 433 healthy healthcare professionals were included and 58.9 % completed the 4 clinical stages of serological assessment. Among adults and elderly people, 25.2 % had chronic diseases (hypertension 50.5 %, diabetes 10 % and obesity 6.5 %). Most individuals have 95 % protection in the first 3 months after the second dose, and 67.68 % protection after 6 months. Total antibodies ranged from 3 to 10 on the reactivity index, and the anti-RBD IgG levels were high. CoronaVac has a 94 % seroconversion rate after 2 doses and can prevent serious cases and outbreaks of the disease, if used on a large scale.

The polymorphism of human leukocyte antigens in the Northeast Asian populations and the lack of broad-spectrum T-cell epitopes covering this cohort markedly limited the development of T cell-directed vaccines against SARS-CoV-2 infection, and also hampered the universal detection of SARS-CoV-2 specific T cells. In this study, 93 CD4+ T-cell epitopes restricted by 12 prevalent HLA-DRB1 allotypes, which covering over 80% Chinese and Northeast Asian populations, were identified from the S, E, M, N and RdRp proteins of SARS-CoV-2 by in silico prediction, DC-peptide-PBL coculture experiment, and immunization in HLA-A2/DR1 transgenic mice. Furthermore, by using validated 215 CD8+ T cell epitope peptides and 123 CD4+ T-cell epitope peptides covering Northeast Asian cohort, the universal ELISpot detection systems of SARS-CoV-2 specific CD8+ T cells and CD4+ T cells were established, for the first time, and followed by the tests for 50 unexposed and 100 convalescent samples. The median of spot-forming units for CD8+ T cells and CD4+ T cells were 68 and 15, respectively, in the unexposed donors, but were 137 and 52 in the convalescent donors 6 months after recovery while 128 and 47 in the convalescent donors 18 months after recovery. This work initially provided the broad-spectrum CD4+ T-cell epitope library of SARS-CoV-2 for the design of T cell-directed vaccines and the universal T cell detection tool tailoring to Northeast Asian population, and confirmed the long-term memory T cell immunity after SARS-CoV-2 infection.

There are mixed findings in the literature regarding the association between HIV status and the risk of COVID-19 infection. Thus, we aimed to estimate the association between characteristics of HIV infection and the risk of COVID-19 Infection in a Chinese sample.

We conducted a cross-sectional survey of 1995 people living with HIV (PLWH) and 3503 HIV-negative adults in Ningbo, China. We compared the prevalence rates of the SARS-CoV-2 infection and the long nucleic acid conversion time (more than 2 weeks) among PLWH and HIV-negative participants, respectively. In addition, we explored the risk factors associated with SARS-CoV-2 infection and the long nucleic acid conversion time among the two groups.

Overall, 1485/1995 (74.4%) PLWH and 2864/3503 (81.8%) HIV-negative people were infected with SARS-CoV-2. Among the SARS-CoV-2-infected participants, 437/1485 (29.4%) PLWH and 649/2864 (22.7%) HIV-negative people had the long nucleic acid conversion time. After controlling for the potential confounders, the rate of the SARS-CoV-2 infection was lower among the PLWH than the HIV-negative group (adjusted OR = 0.836, 95% CI = 0.706-0.990). However, PLWH had a significantly higher risk of the long nucleic acid conversion time after the SARS-CoV-2 infection (adjusted OR = 1.417, 95% CI = 1.176-1.707) than the HIV negative participants. Compared with those who did not receive ART, PLWH adults who received ART significantly had the increased risk of SARS-CoV-2 infection. Furthermore, HIV-negative participants receiving COVID-19 vaccines significantly displayed the decreased likelihood of the long nucleic acid conversion time after the SARS-CoV-2 infection.

Our study indicates that different HIV Infection status was significantly and differently associated with the SARS-CoV-2 infection and the long nucleic acid conversion time. However, the further studies are needed to confirm the effect of ART and COVID-19 vaccines on SARS-CoV-2 infection in PLWH.

Three years into the SARS-CoV-2 pandemic, the virus continues to mutate despite widespread vaccination, posing ongoing challenges for epidemic prevention and control. The relationship between viral shedding and immune escape remains under investigation. This study aims to examine the association between viral shedding and immune escape in the BA.4/5 and BF.7 variants.

We included 542 patients infected with the Omicron variant from Beijing Xiaotangshan shelter hospital. Based on the viral strain, patients were divided into BA.4/5 group and BF.7 group. Additionally, we categorized patients into rapid viral shedding and slow viral shedding groups according to their viral shedding rates. We explored the relationship between viral shedding and immune-related clinical indicators during this period.

Of the 542 patients, 118 were infected with BA.4/5 variant, and 424 were infected with BF.7 variant. The viral shedding duration differed significantly between BA.4/5 and BF.7 groups (p < 0.0001). However, there was no statistically significant correlation between viral shedding duration and immune-related indicators, such as WBC, Hb, PLT, Neu, Lym, CRP, allergy, fever, and vaccination status (p > 0.05). Furthermore, viral shedding duration was not associated with vaccination status, intervals between vaccinations, or vaccine types (p > 0.05).

The duration of viral shedding in patients infected with Omicron variants BA.4/5 and BF.7 is not associated with WBC, Hb, Lym, CRP, fever, allergy, or vaccine-related indicators. This lack of association may be attributed to immune escape mechanisms.

T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.

Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.

Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]).

The approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.

Humoral immunity plays a critical role in clearing SARS-CoV-2 during viral invasion. However, the proteome-wide characteristics of antibody responses in individuals infected with Omicron variant, both asymptomatic and symptomatic, remain poorly understood. We profiled the serum antibodies from 108 individuals, including healthy controls and those infected with Omicron BA.2, using a SARS-CoV-2 proteome microarray at the amino acid resolution. We constructed a landscape of B-cell epitopes across the SARS-CoV-2 proteome in symptomatic and asymptomatic individuals. Immunodominant epitopes were mainly derived from S, N, Nsp3, M, and ORF3a proteins, with some epitopes overlapping with T-cell epitopes. Using machine learning, we identified a proteomic signature capable of distinguishing asymptomatic individuals from healthy controls in both training and validation cohorts, achieving AUCs of 0.988 and 0.857, respectively. These findings provide crucial immunological insights into BA.2 infections of the Omicron and have implications for future COVID-19 diagnostics and therapeutics.

Virion-mediated outbreaks are imminent and despite rapid responses, continue to cause adverse symptoms and death. Therefore, tunable, sensitive, high-throughput assays are needed to help diagnose future virion-mediated outbreaks. Herein, it is developed a tunable in situ assay to selectively enrich virions and extracellular vesicles (EVs) and simultaneously detect antigens and nucleic acids at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA) enhanced sensitivities compared to quantitative reverse-transcription polymerase chain reaction (qRT-PCR), enabling the detection of virions in asymptomatic patients, genetic mutations in single virions, and enabling the continued long-term expression of viral RNA in the EV-enriched subpopulation in the plasma of patients with post-acute sequelae of the coronavirus disease of 2019 (COVID-19). BARA revealed highly accurate diagnoses of COVID-19 by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA in saliva and nasopharyngeal swab samples. Altogether, the single-particle detection of antigens and viral RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks.

Mathematical models of viral dynamics are crucial in understanding infection trajectories. However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load data often includes limited sparse observations with significant heterogeneity. This study aims to: (1) understand the impact of patient characteristics in shaping the temporal viral load trajectory and (2) establish a data collection protocol (DCP) to reliably reconstruct individual viral load trajectories. We collected longitudinal viral load data for SARS-CoV-2 Delta and Omicron variants from 243 patients in Singapore (2021-2022). A viral dynamics model was calibrated using patients' age, symptom presence, and vaccination status. We accessed associations between these patient characteristics and aspects of viral dynamics using linear regression models. We evaluated the accuracy of viral load trajectory estimation under different simulated DCPs by varying patient numbers, test frequencies, and test intervals. Older unvaccinated individuals had a longer viral shedding duration due to lower infection and cell death rates. Higher peak viral loads were found in older, symptomatic, and vaccinated individuals, with earlier peaks in younger vaccinated individuals. Symptom presence and vaccination resulted in a shorter time from infection to diagnosis. To accurately estimate viral dynamics, more frequent tests, longer test intervals, and larger patient samples are required. For 500 patients, a 21-day follow-up with measurements every 3 days and an 8-day follow-up with daily measurements was optimal for the Delta and Omicron variants, respectively. Patient characteristics significantly impacted viral dynamics. Our analytic approach and recommended DCPs can enhance preparedness and response to emerging pathogens beyond SARS-CoV-2.

Persistent multi-organ symptoms after coronavirus disease 2019 (COVID-19) have been termed "long COVID" or "post-acute sequelae of SARS-CoV-2 infection." The complexity of these clinical manifestations posed challenges early in the pandemic as different ambulatory models formed out of necessity to manage the influx of patients. Little is known about the characteristics and outcomes of patients seeking care at multidisciplinary post-COVID centers.

We performed a retrospective cohort study of patients evaluated at our multidisciplinary comprehensive COVID-19 center in Chicago, Ill, between May 2020 and February 2022. We analyzed specialty clinic utilization and clinical test results according to severity of acute COVID-19.

We evaluated 1802 patients a median of 8 months from acute COVID-19 onset, including 350 post-hospitalization and 1452 non-hospitalized patients. Patients were seen in 2361 initial visits in 12 specialty clinics, with 1151 (48.8%) in neurology, 591 (25%) in pulmonology, and 284 (12%) in cardiology. Among the patients tested, 742/916 (81%) reported decreased quality of life, 284/553 (51%) had cognitive impairment, 195/434 (44.9%) had alteration of lung function, 249/299 (83.3%) had abnormal computed tomography chest scans, and 14/116 (12.1%) had elevated heart rate on rhythm monitoring. Frequency of cognitive impairment and pulmonary dysfunction was associated with severity of acute COVID-19. Non-hospitalized patients with positive SARS-CoV-2 testing had findings similar to those with negative or no test results.

The experience at our multidisciplinary comprehensive COVID-19 center shows common utilization of multiple specialists by long COVID patients, who harbor frequent neurologic, pulmonary, and cardiologic abnormalities. Differences in post-hospitalization and non-hospitalized groups suggest distinct pathogenic mechanisms of long COVID in these populations.