scholarly journals Dynamic change and clinical relevance of post-infectious SARS-CoV-2 antibody responses

2021 ◽  
Author(s):  
PWG Mallon ◽  
W Tinago ◽  
A Garcia Leon ◽  
K McCann ◽  
G Kenny ◽  
...  
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Post Infection ◽  
Dynamic Change ◽  
Severe Disease ◽  
Additive Models ◽  
Antibody Responses ◽  
Rapid Decline ◽  
Relative Differences ◽  
Post Infectious

AbstractBackgroundAlthough reports suggest that most individuals with COVID-19 develop detectable antibodies post infection, the kinetics, durability, and relative differences between IgM and IgG responses beyond the first few weeks after symptom onset remain poorly understood.MethodsWithin a large, well-phenotyped, diverse, prospective cohort of subjects with and without SARS-CoV-2 PCR-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity and specificity, relationship with disease severity and mapped the kinetics of antibody responses over time using generalised additive models.ResultsWe analysed 1,001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1-47.1%) early (<10 days) after symptom onset but increased to >80% after 10 days. IgM positivity increased earlier than IgG-targeted assays but positivity peaked between day 32 and 38 post onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analysed, with more rapid decline observed with IgM. Early (<10 days) IgM but not IgG levels were significantly higher in those who subsequently developed severe disease (signal / cut-off 4.20 (0.75-17.93) versus 1.07 (0.21-5.46), P=0.048).ConclusionsThis study suggests that post-infectious antibody responses in those with confirmed COVID-19 begin to decline relatively early post infection and suggests a potential role for higher IgM levels early in infection predicting subsequent disease severity.

scholarly journals Dynamic change and clinical relevance of post-infectious SARS-CoV-2 antibody responses

2021 ◽  
Author(s):  
P W G Mallon ◽  
W Tinago ◽  
A Garcia Leon ◽  
K McCann ◽  
G Kenny ◽  
...  
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Post Infection ◽  
Dynamic Change ◽  
Severe Disease ◽  
Additive Models ◽  
Antibody Responses ◽  
Rapid Decline ◽  
Relative Differences ◽  
Post Infectious

Abstract Background Although reports suggest that most individuals with COVID-19 develop detectable antibodies post infection, the kinetics, durability, and relative differences between IgM and IgG responses beyond the first few weeks after symptom onset remain poorly understood. Methods Within a large, well-phenotyped, diverse, prospective cohort of subjects with and without SARS-CoV-2 PCR-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity and specificity, relationship with disease severity and mapped the kinetics of antibody responses over time using generalised additive models. Results We analysed 1,001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1-47.1%) early (&lt;10 days) after symptom onset but increased to &gt;80% after 10 days. IgM positivity increased earlier than IgG-targeted assays but positivity peaked between day 32 and 38 post onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analysed, with more rapid decline observed with IgM. Early (&lt;10 days) IgM but not IgG levels were significantly higher in those who subsequently developed severe disease (signal / cut-off 4.20 (0.75-17.93) versus 1.07 (0.21-5.46), P=0.048). Conclusions This study suggests that post-infectious antibody responses in those with confirmed COVID-19 begin to decline relatively early post infection and suggests a potential role for higher IgM levels early in infection predicting subsequent disease severity

scholarly journals Association between incubation period and clinical characteristics of patients with COVID-19

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095683
Author(s):  
Yeyu Cai ◽  
Jiayi Liu ◽  
Haitao Yang ◽  
Mian Wang ◽  
Qingping Guo ◽  
...  
Keyword(s):  
Incubation Period ◽  
Disease Severity ◽  
Symptom Onset ◽  
Clinical Characteristics ◽  
Characteristic Curve ◽  
Severe Disease ◽  
Receiver Operator Characteristic Curve ◽  
Hunan Province ◽  
Laboratory Findings ◽  
Incubation Periods

Purpose To investigate associations between the clinical characteristics and incubation periods of patients infected with coronavirus disease 2019 (COVID-19) in Wuhan, China. Methods Complete clinical and epidemiological data from 149 patients with COVID-19 at a hospital in Hunan Province, China, were collected and retrospectively analyzed. Results Analysis of the distribution and receiver operator characteristic curve of incubation periods showed that 7 days was the optimal cut-off value to assess differences in disease severity between groups. Patients with shorter (≤7 days) incubation periods (n = 79) had more severe disease, longer durations of hospitalization, longer times from symptom onset to discharge, more abnormal laboratory findings, and more severe radiological findings than patients with longer (>7 days) incubation periods. Regression and correlation analyses also showed that a shorter incubation period was associated with longer times from symptom onset to discharge. Conclusion The associations between the incubation periods and clinical characteristics of COVID-19 patients suggest that the incubation period may be a useful marker of disease severity and prognosis.

scholarly journals Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes

2021 ◽  
Vol 12 ◽  
Author(s):  
Mei-Yi Lu ◽  
Ya-Lin Lin ◽  
Yali Kuo ◽  
Chi-Fen Chuang ◽  
Jen-Ren Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Post Infection ◽  
Early Stage ◽  
Dynamic Change ◽  
Severe Disease ◽  
Enterovirus 71 ◽  
Ev71 Infection ◽  
Structural Defects ◽  
Neurological Involvement ◽  
Inflammatory Macrophages

Enterovirus 71 (EV71) is a positive single-stranded RNA virus from the enterovirus genus of the Picornaviridae family. Most young children infected with EV71 develop mild symptoms of hand, foot and mouth disease, but some develop severe symptoms with neurological involvement. Limb paralysis from EV71 infection is presumed to arise mainly from dysfunction of motor neurons in the spinal cord. However, EV71 also targets and damages skeletal muscle, which may also contribute to the debilitating symptoms. In this study, we have delineated the impacts of EV71 infection on skeletal muscle using a mouse model. Mouse pups infected with EV71 developed limb paralysis, starting at day 3 post-infection and peaking at day 5-7 post-infection. At later times, mice recovered gradually but not completely. Notably, severe disease was associated with high levels of myositis accompanied by muscle calcification and persistent motor end plate abnormalities. Interestingly, macrophages exhibited a dynamic change in phenotype, with inflammatory macrophages (CD45+CD11b+Ly6Chi) appearing in the early stage of infection and anti-inflammatory/restorative macrophages (CD45+CD11b+Ly6Clow/-) appearing in the late stage. The presence of inflammatory macrophages was associated with severe inflammation, while the restorative macrophages were associated with recovery. Altogether, we have demonstrated that EV71 infection causes myositis, muscle calcification and structural defects in motor end plates. Subsequent muscle regeneration is associated with a dynamic change in macrophage phenotype.

scholarly journals Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

2020 ◽  
Author(s):  
Frédérique Vernel-Pauillac ◽  
Gerald Murray ◽  
Ben Adler ◽  
Ivo G. Boneca ◽  
Catherine Werts
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Post Infection ◽  
Severe Disease ◽  
Humoral Response ◽  
Antibody Responses ◽  
High Dose ◽  
Leptospira Interrogans ◽  
Homologous Challenge

AbstractLeptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected, zoonotic reemerging disease. Humans are sensitive hosts and may develop severe disease. Some animal species, such as rats and mice can become asymptomatic renal carriers. More than 350 leptospiral serovars have been identified, classified on the basis of the antibody response directed against the lipopolysaccharide (LPS). Similarly to whole inactivated bacteria used as human vaccines, this response is believed to confer only short-term, serogroup-specific protection. The immune response of hosts against leptospires has not been thoroughly studied and correlates of protection would be required to test vaccine candidates. In this work, we studied the immunoglobulin (Ig) profiles in mice infected with L. interrogans over time to determine whether this humoral response confers long-term protection after homologous challenge six months post-infection.Groups of mice were injected intraperitoneally with 2×107 leptospires of one of three pathogenic serovars (Manilae, Copenhageni or Icterohaemorrhagiae), attenuated mutants or heat-killed bacteria. Leptospira-specific immunoglobulin (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection were measured by ELISA. Strikingly, we found sustained high levels of IgM in mice infected with the pathogenic Manilae and Copenhageni strains, both colonizing the kidney. In contrast, the Icterohaemorrhagiae strain did not lead to kidney colonization, even at high dose, and triggered a classical IgM response that peaked at day 8 post-infection and disappeared. The virulent Manilae and Copenhageni serovars elicited high levels and similar profiles of IgG subclasses in contrast to Icterohaemorrhagiae strains that stimulated weaker antibody responses. Inactivated heat-killed Manilae strains elicited very low responses. However, all mice pre-injected with leptospires challenged with high doses of homologous bacteria did not develop acute leptospirosis, and all antibody responses were boosted after challenge. Furthermore, we showed that 2 months post challenge, mice pre-infected with the M895 Manilae LPS mutant or heat-killed bacterin were completely protected against renal colonization. In conclusion, we observed a sustained IgM response potentially associated with chronic leptospiral renal infection. We also demonstrated in mice different profiles of protective antibody response after L. interrogans infection, depending on the serovar and virulence of strains.Author summaryLeptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected zoonotic reemerging disease. The immune response of hosts against these bacteria has not been thoroughly studied. Here, we studied over 6 months the immunoglobulin (Ig) profiles in mice infected with L. interrogans and determined whether this humoral response confers long-term protection after homologous challenge six months after primary infection. Groups of mice were infected intraperitoneally with 2×107 bacteria of one of three different pathogenic serovars (Manilae, Copenhageni and Icterohaemorrhagiae) and some corresponding attenuated avirulent mutants. We measured by ELISA each type of Leptospira-specific Ig (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection. We showed different profiles of antibody response after L. interrogans challenge in mice, depending on the serovar and virulence of strains. However, all infected mice, including the ones harboring low antibody levels, like mice vaccinated with an inactivated, heat-killed strain, were protected against leptospirosis after challenge. Notably, we also showed an unusual sustained IgM response associated with chronic leptospiral colonization. Altogether, this long-term immune protection is different from what is known in humans and warrants further investigation.

scholarly journals Dynamic changes in the immune response correlate with disease severity and outcomes during infection with SARS-CoV-2

2020 ◽  
Author(s):  
Fang Zheng ◽  
Ruochan Chen ◽  
Run Yao ◽  
Yaxiong Huang ◽  
Ning Li ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Disease Severity ◽  
Dynamic Change ◽  
Severe Disease ◽  
Underlying Disease ◽  
Dynamic Changes ◽  
Th Cells ◽  
Lower Baseline ◽  
Kinetics Of

Abstract Background:The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout China and all over the world. Little is known about the dynamic changes in the patient immune responses to SARS-CoV-2, and how different responses are correlated with disease severity and outcomes.Method:74 patients with confirmed COVID-19 were enrolled in this prospective research. The demographic information, medical history, symptoms, signs and laboratory results were analyzed and compared between severe and non-severe patients. The leukocytes, lymphocyte subsets and inflammatory cytokines were longitudinally collected.Results:Of the 74 patients included, 17 suffered from severe disease. The severe patients tended be older (65.29 ± 12.33 years vs. 45.37 ± 18.66 years), and had a greater degree of underlying disease (41.18% vs. 24.56%) , lower baseline lymphocytes counts (0.69 ± 0.36 × 10⁹ vs. 1.46 ± 0.75 × 10⁹) , higher neutrophil-lymphocyte-ratios (NLRs; 3.76 (3.15–5.51) vs. 2.07 (1.48–2.93)) and lower baseline eosinophil counts (0.01 ± 0.01 × 10⁹ vs. 0.05 ± 0.07 × 10⁹), than that in non-severe patients. The baseline helper T (Th) cells (335.47 vs. 666.46/mL), suppressor T(Ts) cells (158 vs. 334/mL), B cells (95 vs. 210/mL), and natural killer (NK) cells (52 vs. 122/mL) were significantly decreased in severe cases compared to that in non-severe cases. In addition, the baseline neutrophils and B cells were positively correlated with the severity of COVID-19 and the baseline lymphocytes and Th cells were negatively correlated with the severity of COVID-19. The dynamic change of T cells, Th cells and IFN-γ in the severe cases were parallel to the amelioration of the disease.Conclusions:Collectively, our study provides novel information on the kinetics of the immune responses in a cohort of COVID-19 patients with different disease severities. Furthermore, our study indicates that both innate and adaptive immune responses correlate with better clinical outcomes.

scholarly journals Airway antibodies wane rapidly after COVID-19 but B cell memory is generated across disease severity

2020 ◽  
Author(s):  
Alberto Cagigi ◽  
Meng Yu ◽  
Sara Falck-Jones ◽  
Sindhu Vangeti ◽  
Björn Österberg ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Disease Severity ◽  
Severe Disease ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Full Spectrum ◽  
Viral Spread ◽  
Specific Memory

AbstractUnderstanding immune responses following SARS-CoV-2 infection in relation to COVID-19 severity is critical for predicting the effects of long-term immunological memory on viral spread. Here we longitudinally assessed systemic and airway immune responses against SARS-CoV-2 in a well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity; from asymptomatic infection to fatal disease. High systemic and airway antibody responses were elicited in patients with moderate to severe disease, and while systemic IgG levels were maintained after acute disease, airway IgG and IgA declined significantly. In contrast, individuals with mild symptoms showed significantly lower antibody responses but their levels of antigen-specific memory B cells were comparable with those observed in patients with moderate to severe disease. This suggests that antibodies in the airways may not be maintained at levels that prevent local virus entry upon re-exposure and therefore protection via activation of the memory B cell pool is critical.SummaryCOVID-19 severity determines the level of systemic and airway IgG and IgA but while IgG are maintained in plasma during convalescence, antibodies wane rapidly in the airways.However, comparable levels of antigen-specific memory B cells are generated across disease severity.

scholarly journals SARS-CoV-2 Antibody responses do not predict COVID-19 disease severity

2020 ◽  
Author(s):  
William S. Phipps ◽  
Jeffrey A. SoRelle ◽  
Quan-Zhen Li ◽  
Lenin Mahimainathan ◽  
Ellen Araj ◽  
...  
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Severe Disease ◽  
Cross Reactivity ◽  
Reactivity Index ◽  
Disease Course ◽  
Igg Antibodies ◽  
Previous Diagnosis ◽  
Healthy Donors ◽  
Antibody Levels

Background: Initial reports indicate adequate performance of some serological-based SARS-CoV-2 assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course. Methods: In this study, a total of 968 subjects were tested for IgG antibodies reactive to SARS-CoV-2. We confirmed analytic specificity using 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for PCR-based respiratory viral panel. One-hundred seventy-three cases of confirmed or suspected SARS-CoV-2 were tested for IgG. A subgroup of 37 SARS-CoV-2 PCR-positive cases was tested for nucleocapsid-specific IgM antibody using an in-house developed microarray method. Antibody levels were compared between disease severity groups. Results: All specificity specimens were negative for SARS-CoV-2 IgG antibodies (0/656, 0%). Cross reactivity was not detected in specimens with antinuclear antibodies and rheumatoid factor, or cases with previous diagnosis of viral infection including human coronavirus. Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels. Conclusions: The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Index values of IgG and IgM antibodies did not predict disease severity in our patient population.

scholarly journals Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

2021 ◽  
Vol 15 (3) ◽  
pp. e0008970
Author(s):  
Frédérique Vernel-Pauillac ◽  
Gerald L. Murray ◽  
Ben Adler ◽  
Ivo G. Boneca ◽  
Catherine Werts
Keyword(s):  
Post Infection ◽  
Severe Disease ◽  
Humoral Response ◽  
Antibody Responses ◽  
High Dose ◽  
Specific Igg ◽  
High Doses ◽  
Rats And Mice ◽  
Renal Infection

Leptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected, zoonotic reemerging disease. Humans are sensitive hosts and may develop severe disease. Some animal species, such as rats and mice can become asymptomatic renal carriers. More than 350 leptospiral serovars have been identified, classified on the basis of the antibody response directed against the lipopolysaccharide (LPS). Similarly to whole inactivated bacteria used as human vaccines, this response is believed to confer only short-term, serogroup-specific protection. The immune response of hosts against leptospires has not been thoroughly studied, which complicates the testing of vaccine candidates. In this work, we studied the immunoglobulin (Ig) profiles in mice infected with L. interrogans over time to determine whether this humoral response confers long-term protection after homologous challenge six months post-infection. Groups of mice were injected intraperitoneally with 2×107 leptospires of one of three pathogenic serovars (Manilae, Copenhageni or Icterohaemorrhagiae), attenuated mutants or heat-killed bacteria. Leptospira-specific immunoglobulin (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection were measured by ELISA. Strikingly, we found sustained high levels of IgM in mice infected with the pathogenic Manilae and Copenhageni strains, both colonizing the kidney. In contrast, the Icterohaemorrhagiae strain did not lead to kidney colonization, even at high dose, and triggered a classical IgM response that peaked at day 8 post-infection and disappeared. The virulent Manilae and Copenhageni serovars elicited high levels and similar profiles of IgG subclasses in contrast to Icterohaemorrhagiae strains that stimulated weaker antibody responses. Inactivated heat-killed Manilae strains elicited very low responses. However, all mice pre-injected with leptospires challenged with high doses of homologous bacteria did not develop acute leptospirosis, and all antibody responses were boosted after challenge. Furthermore, we showed that 2 months post challenge, mice pre-infected with the attenuated M895 Manilae LPS mutant or heat-killed bacterin were completely protected against renal colonization. In conclusion, we observed a sustained IgM response potentially associated with chronic leptospiral renal infection. We also demonstrated in mice different profiles of protective and cross-reactive antibodies after L. interrogans infection, depending on the serovar and virulence of strains.

scholarly journals Severity of bovine tuberculosis is associated with innate immune-biased transcriptional signatures of whole blood in early weeks after experimental Mycobacterium bovis infection

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0239938
Author(s):  
Jayne E. Wiarda ◽  
Paola M. Boggiatto ◽  
Darrell O. Bayles ◽  
W. Ray Waters ◽  
Tyler C. Thacker ◽  
...  
Keyword(s):  
Disease Severity ◽  
Mycobacterium Bovis ◽  
Whole Blood ◽  
Post Infection ◽  
Bovine Tuberculosis ◽  
Severe Disease ◽  
Clinical Status ◽  
Cell Types ◽  
Innate Immune ◽  
Infected Cattle

Mycobacterium bovis, the causative agent of bovine tuberculosis, is a pathogen that impacts both animal and human health. Consequently, there is a need to improve understanding of disease dynamics, identification of infected animals, and characterization of the basis of immune protection. This study assessed the transcriptional changes occurring in cattle during the early weeks following a M. bovis infection. RNA-seq analysis of whole blood-cell transcriptomes revealed two distinct transcriptional clusters of infected cattle at both 4- and 10-weeks post-infection that correlated with disease severity. Cattle exhibiting more severe disease were transcriptionally divergent from uninfected animals. At 4-weeks post-infection, 25 genes had commonly increased expression in infected cattle compared to uninfected cattle regardless of disease severity. Ten weeks post-infection, differential gene expression was only observed when severely-affected cattle were compared to uninfected cattle. This indicates a transcriptional divergence based on clinical status following infection. In cattle with more severe disease, biological processes and cell type enrichment analyses revealed overrepresentation of innate immune-related processes and cell types in infected animals. Collectively, our findings demonstrate two distinct transcriptional profiles occur in cattle following M. bovis infection, which correlate to clinical status.

scholarly journals Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19

2020 ◽  
Author(s):  
Xiangyu Chen ◽  
Zhiwei Pan ◽  
Shuai Yue ◽  
Fei Yu ◽  
Junsong Zhang ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Positive Correlation ◽  
Asymptomatic Patients ◽  
Neutralizing Capacity

COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.

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