Post-symptom Onset Research Articles

Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Relationship between Acute-Phase Symptoms and Immunoglobulin G Seropositivity up to Eight Months after COVID-19.

Background and Objectives: Given the limited knowledge of antibody responses to COVID-19 and their determinants, we analyzed the relationship between the occurrence of acute-phase symptoms and infection-induced immunoglobulin (Ig) G seropositivity up to 8 months post-symptom onset. Materials and Methods: In this cross-sectional study, 661 middle-aged unvaccinated healthcare workers (HCWs) were interviewed about the presence of symptoms during the acute phase of their previously confirmed COVID-19 and were tested for specific IgG, targeting the spike protein (S1 and S2). The dependence of seropositivity on the symptom occurrence was explored through multiple logistic regression, adjusted for the interval between symptom onset and serology testing, and through classification and regression trees. Results: A total of 551 (83.4%) HCWs showed seropositivity and, inversely, 110 (16.6%) HCWs were seronegative. The chance of IgG seropositivity was increased by dyspnea (odds ratio (OR) 1.48, p < 0.001) and anosmia (OR 1.52, p = 0.021). Fever in HCWs with dyspnea resulted in the highest detected seropositivity rate, and anosmia in HCWs without dyspnea significantly increased the proportion of seropositivity. Conclusion: Clinical manifestation of the acute phase of COVID-19 predisposes to the development of infection-induced antibody responses. The findings can be applied for assessing the long-term protection by IgG, and thus, for creating effective surveillance strategies.

Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

PurposeSix to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions.MethodsWe analyzed sera of 430 COVID-19 patients from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome.ResultsThe prevalence of neutralizing AABs to IFN-α and IFN-ω in COVID-19 patients from all cohorts was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected (max. WHO score 6–8), predominantly male (83%) patients (7.6%, 18/237 for IFN-α-AABs and 4.6%, 11/237 for IFN-ω-AABs in 237 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with lower probability of survival (7.7% versus 80.9% in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE.ConclusionIFN-AABs may serve as early biomarker for the development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.

Assessing mucosal antibody responses to SARS-CoV-2 in humans and mice.

Abstract COVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We previously developed an enzyme-linked immunosorbent assay (ELISA) protocol to profile antibody responses to the SARS-CoV-2 Spike protein and its receptor-binding domain (RBD) in the saliva of patients with COVID-19. Anti-SARS-CoV-2 antibody responses were readily detected in saliva, peaking at 16–30 days post-symptom onset. While anti-SARS-CoV-2 IgM/IgA were found to decay, IgG responses were more long-lived, persisting up to 105 days. Now we wish to know (1) if anti-SARS-CoV-2 antibodies are generated locally in the oral cavity, (2) the relative kinetics of IgA versus IgG appearance in the oral cavity, and (3) whether salivary antibodies have the capacity to neutralize SARS-CoV-2. To answer these, I have adapted our ELISA to detect secretory component-associated SARS-CoV-2-specific antibodies. I found that 33.3% and 26.9% of COVID-19 patients were positive for secretory component-associated antibodies to Spike and RBD, respectively. Secretory component-associated antibodies correlated with antigen-specific IgA levels, particularly for the Spike antigen. Moreover, using saliva from contact-traced subjects, I found that anti-Spike/RBD IgM/IgA are detected in the saliva 7 days post-exposure, prior to IgG. Lastly, I detected Spike-specific antibody-secreting cells in lymphoid tissues draining the upper respiratory tract upon intranasal infection of K18-hACE2 mice with a non-lethal dose of SARS-CoV-2. In summary, I have provided evidence in humans and mice that a local antibody response that quickly class switches to IgA occurs in the oral cavity and draining lymph nodes upon infection with SARS-CoV-2.

Long-term persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific and neutralizing antibodies in recovered COVID-19 patients.

Understanding antibody responses after natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can guide the coronavirus disease 2019 (COVID-19) vaccine schedule, especially in resource-limited settings. This study aimed to assess the dynamics of SARS-CoV-2 antibodies, including anti-spike protein 1 (S1) immunoglobulin (Ig)G, anti-receptor-binding domain (RBD) total Ig, anti-S1 IgA, and neutralizing antibody against wild-type SARS-CoV-2 over time in a cohort of patients who were previously infected with the wild-type SARS-CoV-2. Between March and May 2020, 531 individuals with virologically confirmed cases of wild-type SARS-CoV-2 infection were enrolled in our immunological study. Blood samples were collected at 3-, 6-, 9-, and 12-months post symptom onset or detection of SARS-CoV-2 by RT-PCR (in asymptomatic individuals). The neutralizing titers against SARS-CoV-2 were detected in 95.2%, 86.7%, 85.0%, and 85.4% of recovered COVID-19 patients at 3, 6, 9, and 12 months after symptom onset, respectively. The seropositivity rate of anti-S1 IgG, anti-RBD total Ig, anti-S1 IgA, and neutralizing titers remained at 68.6%, 89.6%, 77.1%, and 85.4%, respectively, at 12 months after symptom onset. We observed a high level of correlation between neutralizing and SARS-CoV-2 spike protein-specific antibody titers. The half-life of neutralizing titers was estimated at 100.7 days (95% confidence interval = 44.5–327.4 days, R2 = 0.106). These results support that the decline in serum antibody levels over time in both participants with severe disease and mild disease were depended on the symptom severity, and the individuals with high IgG antibody titers experienced a significantly longer persistence of SARS-CoV-2-specific antibody responses than those with lower titers.

443 COVID19 disease severity influences the expression of markers of durability in memory B cells

OBJECTIVES/GOALS: Studies have shown that SARS-CoV-2 specific memory B cells can be maintained at least a year after exposure. However, reports show an altered B cell response during infection in severe COVID-19 cases. This study aims to describe the B cell response during COVID-19 convalescence with a focus on signatures that contribute to durable and robust immunity. METHODS/STUDY POPULATION: Our study cohort consisted of individuals who had recovered from non-severe (hospitalized) or severe (hospitalized and requiring invasive mechanical ventilation) COVID-19. In our comparative analysis, samples from both groups were carefully matched to fall within 4-5 weeks post-symptom onset. We also performed a longitudinal analysis of non-severe patients with sampling ending 5 months post-symptom onset. Using high parameter flow cytometry, we characterized the phenotype of memory B cells using 19 distinct cell markers and fluorescently labeled probes to identify B cells reactive with SARS-CoV-2 spike and receptor-binding domain protein. Additionally, serum collected from individuals was used to quantify antibody titers. RESULTS/ANTICIPATED RESULTS: The frequency of spike-specific B cells and serum antibody titers were similar between severe and non-severe groups. However, we observed that individuals recovered from severe COVID-19 have a significantly reduced frequency of spike specific IgG+ memory B cells expressing Tbet and FcRL5 (markers associated with long lived immunity). In the non-severe patients, we observed IgG+Tbet+ B cells targeting the spike protein peak at 2-3 weeks post-symptom onset, decrease by almost fifty percent 4-5 weeks post-symptom onset, and return to baseline 5 months post-symptom onset. Our study also validated previous findings of a short-lived primary response of IgM+ B cells targeting the spike protein. DISCUSSION/SIGNIFICANCE: Our findings highlight potential implications for long-term immunity against re-infection or severity of the resulting disease in patients with severe COVID-19. Further investigation will be necessary to determine whether the maintenance of immunological protection is hindered in patients who overcame severe COVID-19.

Characterisation of Dynamiker SARS-Cov-2 Neutralization Antibody (Nabs) Lateral Flow Immunoassay (LFA) and Enzyme Immunoassays (Eias) Diasorin Liaison RBD and Abbott Igg Quant in Convalescent Sera of SARS-Cov-2 Patients

The EIAs (enzyme immunoassays) that react with the SARS-CoV-2 RBD protein and Spike protein such as DiaSorin S1/S2 IgG and Abbott II IgG correlate very well with neutralizing antibodies. LFAs (lateral flow assays) are the fastest and most convenient tests usually performed within 10 – 15 minutes. Several LFAs have been commercialized to detect IgG, IgM antibodies. In this short report we characterised the Dynamiker SARS-CoV-2 neutralising antibodies (Nabs) LFA with EIAs (DiaSorin Liaisons SARS-CoV-2 RBD antibodies and Abbotts IgG spike antibodies) in the sera of Covid-19 convalescent patients (40 – 93 days) post onset of symptoms. The EIAs (DiaSorin Liaisons SARS-CoV-2 RBD antibodies and Abbotts IgG spike antibodies) were detected in the sera of all the Covid-19 convalescent patients (100%), while the LFA Dynamiker SARS-Cov-2 Nabs were found in the sera of 86% of Covid-19 convalescent patients.&nbsp; In addition, the Dynamiker SARS-CoV-2 Nabs lateral flow immunoassay (LFA) had a positive correlation with the DiaSorin Liaison (RBD) and Abbott IgG Quant (Spike) antibody assays.

C-DU(KE) Calculator: A Clinical Tool for Risk Stratification in Infectious Keratitis.

The aim of this study was to identify characteristics of infectious keratitis predictive of poor outcome to develop a web-based predictive calculator. A retrospective chart review was performed at the Duke Eye Center. Two hundred fifteen adult patients with culture-proven infectious keratitis presenting between January 1, 2016, and December 31, 2020, were separated into a derivation set (136 patients, 53 positives; 83 controls) and a temporal validation set (79 patients, 26 positives; 53 controls). The poor outcome group consisted of patients requiring penetrating keratoplasty for visually significant scarring, penetrating keratoplasty for ulcer progression, or evisceration/enucleation for endophthalmitis. Univariable analysis was performed followed by stepwise multivariable logistic regression to obtain a predictive model in the derivation data set. Culture-naïve and postculture models were constructed. Discrimination and calibration were assessed using the area under the curve (AUC) and calibration plots, respectively. The culture-naïve model consisted of corticosteroid drop use postsymptom onset [Odds Ratio (OR) = 2.3, P = 0.054], decreased vision (OR = 2.4, P = 0.001), and increased ulcer area (OR = 1.017, P = 0.017). The postculture model additionally included fungal keratitis (OR = 5.4, P = 0.006) and elapsed time from symptoms to organism-sensitive therapy (OR = 1.027, P = 0.014). The models were summarized by the acronym C-DU(KE). The AUCs for the culture-naïve model were 0.794 in the derivation set and 0.850 in the validation set. The AUCs for the postculture model were 0.898 in the derivation set and 0.946 in the validation set. Calibration plots indicated goodness of fit in the data sets for both models. The calculator was deployed under the URL: https://duke-eye-calculator.shinyapps.io/Corneal_Ulcers/ . The C-DU(KE) calculator permits a data-driven prediction of outcome in infectious keratitis that can supplement clinical judgment.

Sensitive and specific serological ELISA for the detection of SARS-CoV-2 infections

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered the worldwide coronavirus disease 2019 (COVID-19) pandemic. Serological assays for the detection of SARS-CoV-2 infections are important to understand the immune response in patients and to obtain epidemiological data about the number of infected people, especially to identify asymptomatic persons not aware of a past infection.MethodsWe recombinantly produced SARS-CoV-2 nucleocapsid (N)-protein in Escherichia coli. We used the purified protein to develop an indirect enzyme-linked immunosorbent assay (ELISA) for the detection of SARS-CoV-2 specific antibodies. This ELISA method was optimized and validated with serum samples collected from 113 patients with RT-PCR-confirmed SARS-CoV-2 infections including hospitalized COVID-19 patients and 1500 control sera mostly collected before 2015 with different clinical background.ResultsThe optimized N-protein-ELISA provided a sensitivity of 89.7% (n = 68) for samples collected from patients with confirmed SARS-CoV-2 infections and mild to severe symptoms more than 14 days after symptom onset or a positive PCR test. The antibody levels remained low for serum samples collected in the first six days (n = 23) and increased in the second week (n = 22) post symptom onset or PCR confirmation. At this early phase, the ELISA provided a sensitivity of 39.1% and 86.4%, respectively, reflecting the time of an IgG immune response against pathogens. The assay specificity was 99.3% (n = 1500; 95% CI 0.995–0.999). Serum samples from persons with confirmed antibody titers against human immunodeficiency viruses 1/2, parvovirus B19, hepatitis A/B virus, cytomegalovirus, Epstein Barr virus, and herpes simplex virus were tested negative.ConclusionsWe conclude that the N-protein-based ELISA developed here is well suited for the sensitive and specific serological detection of SARS-CoV-2 specific IgG antibodies in human serum for symptomatic infections. It may also prove useful to identify previous SARS-CoV-2 infections in vaccinated people, as all currently approved vaccines rely on the SARS-CoV-2 spike (S-) protein.

Evolution of Anti-RBD IgG Avidity following SARS-CoV-2 Infection.

SARS-CoV-2 infection rapidly elicits anti-Spike antibodies whose quantity in plasma gradually declines upon resolution of symptoms. This decline is part of the evolution of an immune response leading to B cell differentiation into short-lived antibody-secreting cells or resting memory B cells. At the same time, the ongoing class switch and antibody maturation processes occurring in germinal centers lead to the selection of B cell clones secreting antibodies with higher affinity for their cognate antigen, thereby improving their functional activity. To determine whether the decline in SARS-CoV-2 antibodies is paralleled with an increase in avidity of the anti-viral antibodies produced, we developed a simple assay to measure the avidity of anti-receptor binding domain (RBD) IgG elicited by SARS-CoV-2 infection. We longitudinally followed a cohort of 29 convalescent donors with blood samples collected between 6- and 32-weeks post-symptoms onset. We observed that, while the level of antibodies declines over time, the anti-RBD avidity progressively increases and correlates with the B cell class switch. Additionally, we observed that anti-RBD avidity increased similarly after SARS-CoV-2 mRNA vaccination and after SARS-CoV-2 infection. Our results suggest that anti-RBD IgG avidity determination could be a surrogate assay for antibody affinity maturation and, thus, suitable for studying humoral responses elicited by natural infection and/or vaccination.

Clinical and analytical evaluation of the Abbott AdviseDx quantitative SARS-CoV-2 IgG assay and comparison with two other serological tests

IntroductionSerological testing is an important tool to assist with assessing the immune response to SARS-CoV-2 infections, the causative agent of COVID-19. A quantitative assay was recently developed by Abbott Laboratories to measures antibodies against the receptor binding domain of the spike protein. In addition to assessing disease prevalence, this assay is useful towards determining the scale and duration of the humoral response to infection and vaccination. Here we evaluated the clinical and analytical performance of the quantitative Abbott AdviseDx SARS-CoV-2 IgG II assay and characterized the longitudinal dynamics of the IgG response against SARS-CoV-2 in 402 infected individuals up to 322 days post-symptom onset. MethodsTo assess test sensitivity, 1257 serum specimens derived from 402 patients positive for SARS-CoV-2 by RT-PCR were analyzed on the Abbott Alinity platform. To evaluate test specificity, 394 specimens were tested from patients who were symptomatic but PCR negative for SARS-CoV-2, as well as 305 archived pre-pandemic samples. To further characterize test performance metrics, we evaluated assay precision and linearity. ResultsThe Abbott AdviseDx SARS-CoV-2 IgG II assay exhibited diagnostic specificity of 99.02% using 305 pre − COVID-19 serum specimens and 98.73% using 394 PCR negative specimens. Using 1257 sequential serum samples collected from PCR-confirmed individuals, clinical test sensitivity of the assay was 39.7% at 3–7 days, 75.9% at 8–14 days, 95.6% at 15–21 days, and 98.7% at 4–5 weeks post-symptom onset. The assay is linear across the analytical measurement range claimed by the manufacturer (22–25,000 AU/mL) and exhibited good analytical precision. The median concentration of IgG increased steadily from <22 AU/mL at 3–7 days post-symptom onset, to a peak of 14,421 AU/mL at 6–7 weeks. Although antibody concentration started to decline at 8–9 weeks following symptom onset, all patients remained seropositive during the observation period. When the positivity rate of this assay was compared with the Abbott anti-NP IgG and EUROIMMUN anti-S1 IgG tests, clinical sensitivity of the Abbott AdviseDx SARS-CoV-2 IgG II assay was the highest at all time points with the exception of 4–5 weeks after symptom onset. ConclusionThe Abbott AdviseDx SARS-CoV-2 IgG II assay offers high test specificity and sensitivity across a broad reportable range. We anticipate this assay will be a useful towards quantitatively assessing the humoral immune response to COVID-19 infection and vaccination.

Long-Term Persistence of Anti-SARS-COV-2 IgG Antibodies.

Antibodies against severe acute respiratory syndrome coronavirus-2 (Anti-SARS-COV-2) can be detected in patients with COVID-19 in 7 to 10 days post onset of symptoms (POS). However, there is no firm evidence of the long-term persistence of these antibodies in recovered COVID-19 patients. Therefore, this study aimed to evaluate the stability of anti-SARS-COV-2 IgG in recovered COVID-19 patients in a 15-month follow-up testing. Thirty hospitalized patients with real-time PCR-confirmed SARS-COV-2 infections were included in the study and five serum samples (1st, 2nd, 3rd, 4th, and 5th) were collected from each participant. The serum levels of N and S specific anti-SARS-COV-2 IgG and IgM antibodies were evaluated by the immunoassay technique at the same time. To determine the correlation between levels of anti-SARS-CoV-2 IgG/IgM with severity of disease, neutrophil-to-lymphocyte ratio (NLR %), and the serum levels of C-reactive protein were evaluated using an automated analyzer and turbidimetry assays, respectively. The mean serum level of anti-SARS-CoV-2 IgG antibody was at the highest level up to 90 days and then decreased significantly 1 year POS (P < 0.0001). However, it was still detectable in a 15-month follow-up testing. There were no significant differences in the mean levels of IgG antibody in patients with mild, moderate, and severe diseases. The results from this study suggest that the titer of anti-SARS-COV-2 IgG antibody is detectable at high levels up to 3 months and then decreases over time. However, these antibodies can be reliably detected in up to 15 months, and they may persist for a long time.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00284-022-02800-0.

Sustained Antibody-Dependent NK Cell Functions in Mild COVID-19 Outpatients During Convalescence.

The coronavirus disease 2019 (COVID19) pandemic has left researchers scrambling to identify the humoral immune correlates of protection from COVID-19. To date, the antibody mediated correlates of virus neutralization have been extensively studied. However, the extent that non-neutralizing functions contribute to anti-viral responses are ill defined. In this study, we profiled the anti-spike antibody subtype/subclass responses, along with neutralization and antibody-dependent natural killer cell functions in 83 blood samples collected between 4 and 201 days post-symptoms onset from a cohort of COVID-19 outpatients. We observed heterogeneous humoral responses against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Overall, anti-spike profiles were characterized by a rapid rise of IgA and sustained IgG titers. In addition, strong antibody-mediated natural killer effector responses correlated with milder disease and being female. While higher neutralization profiles were observed in males along with increased severity. These results give an insight into the underlying function of antibodies beyond neutralization and suggest that antibody-mediated natural killer cell activity is a key function of the humoral response against the SARS-CoV-2 spike protein.

Detection of Newly Secreted Antibodies Predicts Nonrecurrence in Primary Clostridioides difficile Infection.

Within 8 weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no clear clinical correlates or validated biomarkers that can predict recurrence during primary infection. This study demonstrated the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence. Forty-six hospitalized CDI patients were enrolled at Emory University Hospitals. Samples of serum and a novel matrix from circulating plasmablasts called "medium-enriched for newly synthesized antibodies" (MENSA) were collected during weeks 1, 2, and 4. Antibodies specific for 10 C. difficile antigens were measured in each sample. Among the 46 C. difficile-infected patients, 9 (19.5%) experienced recurrence within 8 weeks of primary infection. Among the 37 nonrecurrent patients, 23 (62%; 23/37) had anti-C. difficile MENSA antibodies specific for any of the three toxin antigens: TcdB-CROP, TcdBvir-CROP, and/or CDTb. Positive MENSA responses occurred early (within the first 12 days post-symptom onset), including six patients who never seroconverted. A similar trend was observed in serum responses, but they peaked later and identified fewer patients (51%; 19/37). In contrast, none (0%; 0/9) of the patients who subsequently recurred after hospitalization produced antibodies specific for any of the three C. difficile toxin antigens. Thus, patients with a negative early MENSA response against all three C. difficile toxin antigens had a 19-fold greater relative risk of recurrence. MENSA and serum levels of immunoglobulin A (IgA) and/or IgG antibodies for three C. difficile toxins have prognostic potential. These immunoassays measure nascent immune responses that reduce the likelihood of recurrence thereby providing a biomarker of protection from recurrent CDI. Patients who are positive by this immunoassay are unlikely to suffer a recurrence. Early identification of patients at risk for recurrence by negative MENSA creates opportunities for targeted prophylactic strategies that can reduce the incidence, cost, and morbidity due to recurrent CDI.

Longitudinally monitored immune biomarkers predict the timing of COVID-19 outcomes.

The clinical outcome of SARS-CoV-2 infection varies widely between individuals. Machine learning models can support decision making in healthcare by assessing fatality risk in patients that do not yet show severe signs of COVID-19. Most predictive models rely on static demographic features and clinical values obtained upon hospitalization. However, time-dependent biomarkers associated with COVID-19 severity, such as antibody titers, can substantially contribute to the development of more accurate outcome models. Here we show that models trained on immune biomarkers, longitudinally monitored throughout hospitalization, predicted mortality and were more accurate than models based on demographic and clinical data upon hospital admission. Our best-performing predictive models were based on the temporal analysis of anti-SARS-CoV-2 Spike IgG titers, white blood cell (WBC), neutrophil and lymphocyte counts. These biomarkers, together with C-reactive protein and blood urea nitrogen levels, were found to correlate with severity of disease and mortality in a time-dependent manner. Shapley additive explanations of our model revealed the higher predictive value of day post-symptom onset (PSO) as hospitalization progresses and showed how immune biomarkers contribute to predict mortality. In sum, we demonstrate that the kinetics of immune biomarkers can inform clinical models to serve as a powerful monitoring tool for predicting fatality risk in hospitalized COVID-19 patients, underscoring the importance of contextualizing clinical parameters according to their time post-symptom onset.

Optimal strategies to screen health care workers for COVID-19 in the US: a cost-effectiveness analysis

BackgroundTransmission of SARS-CoV-2 in health care facilities poses a challenge against pandemic control. Health care workers (HCWs) have frequent and high-risk interactions with COVID-19 patients. We undertook a cost-effectiveness analysis to determine optimal testing strategies for screening HCWs to inform strategic decision-making in health care settings.MethodsWe modeled the number of new infections, quality-adjusted life years lost, and net costs related to six testing strategies including no test. We applied our model to four strata of HCWs, defined by the presence and timing of symptoms. We conducted sensitivity analyses to account for uncertainty in inputs.ResultsWhen screening recently symptomatic HCWs, conducting only a PCR test is preferable; it saves costs and improves health outcomes in the first week post-symptom onset, and costs $83,000 per quality-adjusted life year gained in the second week post-symptom onset. When screening HCWs in the late clinical disease stage, none of the testing approaches is cost-effective and thus no testing is preferable, yielding $11 and 0.003 new infections per 10 HCWs. For screening asymptomatic HCWs, antigen testing is preferable to PCR testing due to its lower cost.ConclusionsBoth PCR and antigen testing are beneficial strategies to identify infected HCWs and reduce transmission of SARS-CoV-2 in health care settings. IgG tests’ value depends on test timing and immunity characteristics, however it is not cost-effective in a low prevalence setting. As the context of the pandemic evolves, our study provides insight to health-care decision makers to keep the health care workforce safe and transmissions low.

Detection of IgG and IgM Levels in Patients with COVID-19 in Mosul Province, Iraq

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has become the most dangerous viral infection worldwide. Since its identification in late 2019, the number of medical trials to combat the infection has sharply increased. Here, we investigated the profiles of IgG and IgM in 85 patients with confirmed SARS-CoV-2 infection from day 1 after symptom onset until day 35 with 5-day intervals. Serum samples were collected and stored until use. We observed that IgM levels were detectable on day 5 post symptom onset and increased sharply, with the highest rate detected in moderate cases (32.332 ± 4.32, n=10). Subsequently, a significant reduction in IgM was observed until it was undetectable on day 35 after symptom onset. Meanwhile, IgG levels were detected on day 10 post symptom onset, and the highest rate was observed in moderate cases (8.232 ± 2.3, n=10). A significant increase in IgG rate was observed in all patients, with the highest rate in moderate cases (42.432 ± 4.34, n=67) on day 35 post symptom onset. The statistical difference between the case and control groups was significant (p≤0.001). Two out of 85 patients died during the study.

Should Symptom-based Strategy or Test-based Strategy be Used for Allowing Workers Who were Previously Infected with COVID-19 to Return to Work? A Living Systematic Review

Objective. This review aimed to synthesize data on the accuracy, benefits, and harms of symptom-based and test-based strategies. Methods. A comprehensive search until March 22, 2021, was done in MEDLINE, Cochrane Library, UpToDate,and medrxiv.org, using keywords related to "COVID-19," "symptom-based strategy," and "test-based strategy." Data were qualitatively synthesized. Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results. Eight studies with very low certainty of evidence were included. COVID-19 has not been cultured ten (10) days post-symptom onset in patients with the mild-moderate disease and 21 days post-symptom onset in patients with severe disease. For severely immunocompromised patients, viral shedding was noted several months post-symptom onset. Test-based strategies yielded 40% excess cost, a median of 8 days of excess acute-care-length-of-stay, and ~7.2 excess days-of-work lost compared to symptom-based strategies. A high false negativity rate (98.8%) of RT-PCR was noted among asymptomatic patients. Conclusion. A symptom-based strategy is more cost-effective than a test-based strategy. For workers who had asymptomatic or mild-to-moderate COVID-19, a 10-day symptom-based approach may be indicated. For those who had severe-critical COVID-19, a 21-day symptom-based process is suggested. Conversely, a test-based strategy is recommended for workers who have recovered and are severely immunocompromised.

Characterisation Covid-19 IgG Antibody Kinetics Post Infection and Vaccination using the Boditech iCHROMA™ Fluorescence Immunoassay (FIA) Method

Background: Coronavirus disease 2019 (COVID-19) is an emerging threat affecting millions of people worldwide. This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using the Boditech iCHROMA fluorescence immunoassay (FIA) method. Methods: Samples were collected from 43 subjects and analyzed for IgG antibodies against SARS-CoV-2 using the Boditech iCHROMA FIA. The iCHROMA processes the signal using a cut off index of 0.9 – 1.1, results &lt;0.9 are interpreted as negative, results between 0.9 and 1.1 are interpreted as indeterminate and results &gt;1.1 are interpreted as positive. Longitudinal samples were collected on days between day 1- day 100 post onset of symptoms in 1 subject, single samples collected on days 40-90 post infection in 30 subjects, and single samples collected at 3 time points (pre vaccination, 8-18 days post vaccination and 20-28 days post vaccination) collected from 12 subjects non-infected and previously infected. Results: The Covid-19 IgG concentration was detected (positive and cut off index above 1.1) on day 11 and remained consistently elevated for another 100 days of measurement in the sera of the single infected subject. The IgG cut off indices between day 20 and 100 ranged between 26.8 and 46.7, with a mean of 36.5. In the sera of the 30 patients infected with Covid-19 collected 40 – 90 days post infection, IgG antibodies were detected in all the samples. The IgG cut off indices ranged between 14.0 and 32.60, with a mean of 20.65. Of the twelve subjects who were vaccinated, eight had not been previously infected, while 4 had been previously infected. All 4 (100%) previously infected subjects seroconverted by the first time point (8-18 days post vaccination), whilst only 1/8 (12.5%) of the non-infected subjects seroconverted by the first time point (8-18 days post vaccination). By the second time point (20 - 28 days post vaccination), 2/12 subjects (17%) had failed to seroconvert, whilst 10/12 (83%) of the subjects had seroconverted. In addition, a previously infected subject whose IgG antibodies had dropped to a very low-level, after receiving the first dose of vaccination his IgG antibodies had gone back to his previous antibody levels at the first time point (8-18 days post vaccination). Conclusion: The Boditech iCHROMA FIA method for antibody testing is useful in detecting SARS-CoV-2 in a variety of situations at different time points but has its limitations with regards to determining the difference between previously infected and vaccinated individuals.

Do the Kinetics of Antibody Responses Predict Clinical Outcome in Hospitalized Patients With Moderate-to-Severe COVID-19?

The relationship between the kinetics of antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the severity of Coronavirus Disease 2019 (COVID-19) is poorly understood. The aim of the present study was to investigate whether serum SARS-CoV-2 antibody kinetics serve as an early predictor of clinical deterioration or recovery in hospitalized patients with COVID-19. In this prospective observational study, 102 consecutive patients (median age: 60 years, 58% males) with symptomatic COVID-19 infection diagnosed by real-time polymerase chain reaction assay, hospitalized in two tertiary hospitals, were included. Rapid test for qualitative detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) SARS-CoV-2 antibodies was performed at pre-defined time intervals during hospitalization (days: 0, 3, 7, 10, 14, 21 and 28). During a 3-month follow-up period after COVID-19 disease onset, a total of 87 patients were discharged, 12 patients were intubated and entered the Intensive Care Unit, and three patients died. The median time for seroconversion was 10 days for IgM and 12 days for IgG post onset of symptoms. Univariate logistic regression analysis found no associations between IgM or IgG positivity and clinical outcomes or complications during hospitalization for COVID-19 infection. Diabetes and dyslipidemia were the only clinical risk factors predictive of COVID-19-related complications during hospitalization. SARS-CoV-2 antibody responses do not predict clinical outcome in hospitalized patients with moderate-to-severe COVID-19 infection.