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1.
Journal of Chemical Education ; 99(9):3155, 2022.
Article in English | ProQuest Central | ID: covidwho-2036738

ABSTRACT

The reaction rate and rate law are chemical kinetics concepts that undergraduate students have difficulty understanding and applying in real life. A further challenge is the overall reaction rate of consecutive reactions. Herein we present a creative teaching practice using the analogy-based approach to exploit the similarities between the chemical kinetics of consecutive reactions involved in ethanol oxidation and the model employed to describe the COVID-19 outbreak. Students conducted the mathematical modeling using open online software. Fitting the epidemic data from four different countries during the first wave of the COVID-19 pandemic to the SIR model and comparing the results with the model of ethanol oxidation brought students insight into the effects of kinetic parameters and triggered a discussion on conceptual kinetic fundamentals. This teaching approach sets up an environment where students can build knowledge that accounts for their pandemic experience, fostering mathematical and computational skills along with data analysis and interpretation that promotes a deeper understanding of the phenomena implicated in the kinetics of consecutive reactions. Mathematical modeling activities are here to stay and will continue gaining relevance in undergraduate kinetics courses, even without the lockdown, therefore the development of these kinds of learning strategies is of high significance worldwide.

2.
Front Microbiol ; 13: 856913, 2022.
Article in English | MEDLINE | ID: covidwho-2032801

ABSTRACT

The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as a serious pandemic has altered the global socioeconomic dynamics. The wide prevalence, high death counts, and rapid emergence of new variants urge for the establishment of research infrastructure to facilitate the rapid development of efficient therapeutic modalities and preventive measures. In agreement with this, SARS-CoV-2 strains were isolated from patient swab samples collected during the first COVID-19 wave in Odisha, India. The viral isolates were adapted to in vitro cultures and further characterized to identify strain-specific variations in viral growth characteristics. The neutralization susceptibility of viral isolates to vaccine-induced antibodies was determined using sera from individuals vaccinated in the Government-run vaccine drive in India. The major goal was to isolate and adapt SARS-CoV-2 viruses in cell culture with minimum modifications to facilitate research activities involved in the understanding of the molecular virology, host-virus interactions, drug discovery, and animal challenge models that eventually contribute toward the development of reliable therapeutics.

3.
HemaSphere ; 6:2642-2643, 2022.
Article in English | EMBASE | ID: covidwho-2032108

ABSTRACT

Background: Patients with transfusion-dependent-thalassaemia (TDT) are considered as increased risk population for severe and/or morbid COVID-19 infection. Timely vaccination is the main preventive method for severe COVID-19. Aims: To provide an overview of the clinical profile and outcome of COVID-19 infection in patients with TDT as well as to study the immune response after 3 and 6 months after vaccination against COVID-19 in adult patients with transfusion-dependent thalassaemia. Methods: This analysis focused on the evaluation in TDT patients on the long-term immune response post vaccination and on the course of COVID-19 infection and its correlation with immunization status. Serum was collected at 4 pre-defined time points, namely, just before 1st dose (TP1), 7 weeks after the 1st dose (TP2), 3 months (TP3) and 6 months (TP4) after 2nd dose. Neutralizing antibodies (NAbs) against SARS-CoV-2 were measured using FDA-approved methods. According to manufacturer, the scale of NAbs titer is 0-100%, with ≥30% considered as positive and ≥50% as clinically relevant viral inhibition. Age-matched healthy volunteers (median age: 46 years, range: 24-64 years, 24 males / 53 females) who received mRNA vaccines served as the control group for NAbs evaluation. Results: 340 (170female/170male) TDT patients older than 18 years (mean 43.6±11.5 years) followed in a single unit were included in the analysis. 270 patients (79%) were vaccinated with 2 or 3 doses. Immune response to vaccination was evaluated in 90 patients (median age: 46 years, range: 19-63 years, 40 males / 50 females). NAbs were at the level of non-immunity in all the patients at baseline (TP1) (mean 16.57% ±11.85) and showed a significant increase after the second dose (TP2) mean 86.96%±12.95 (p<0.0001). At TP3 and TP4 Nabs showed a significant decrease but remained in protective levels for the majority of the patients (mean 88.75% ±9.7 and 74.64% ±17.2 respectively(p<0.0001). The kinetics of NAbs were similar to controls except for levels at TP4 (p=0.02) (Figure 1). Up to 10/FEB/2022, 43 TDT patients (median age 43.52 range 18.6-57.9 years) were diagnosed with COVID-19, with 1 of them being infected twice. Of them, 17 were unvaccinated, 18 had received 2 doses of vaccine, while 8 had received 3 doses of the vaccine. The incidence rate was 9.6% and 24.3% for vaccinated and unvaccinated patients, respectively. The severity of the COVID-19 for vaccinated and unvaccinated patients were as follows, respectively, ;Grade 1 (asymptomatic): 0 and 1, Grade 2 (mild symptoms, symptomatic therapy, no COVID19 specific therapy): 23 and 9, Grade 3 (mild symptoms, symptomatic therapy, with COVID19 specific therapy): 1 and 3, Grade 4 (moderate: pneumonia, thrombophlebitis, Hospitalization): 2 and 3, Grade 5 (Hospitalization requiring ICU, death): 0 and 1. Thrombotic event was documented in 1 patient. All patients except one from unvaccinated group are alive. Summary/Conclusion: Immune response to vaccination may wean faster in TDT patients. in Unvaccinated TDT patients were more likely to be infected and to develop more serious COVID-19 infection compared to vaccinated patients. (Figure Presented).

4.
BMC Med ; 20(1):347, 2022.
Article in English | PubMed | ID: covidwho-2029711

ABSTRACT

BACKGROUND: Heterogeneity of the population in relation to infection, COVID-19 vaccination, and host characteristics is likely reflected in the underlying SARS-CoV-2 antibody responses. METHODS: We measured IgM, IgA, and IgG levels against SARS-CoV-2 spike and nucleocapsid antigens in 1076 adults of a cohort study in Catalonia between June and November 2020 and a second time between May and July 2021. Questionnaire data and electronic health records on vaccination and COVID-19 testing were available in both periods. Data on several lifestyle, health-related, and sociodemographic characteristics were also available. RESULTS: Antibody seroreversion occurred in 35.8% of the 64 participants non-vaccinated and infected almost a year ago and was related to asymptomatic infection, age above 60 years, and smoking. Moreover, the analysis on kinetics revealed that among all responses, IgG RBD, IgA RBD, and IgG S2 decreased less within 1 year after infection. Among vaccinated, 2.1% did not present antibodies at the time of testing and approximately 1% had breakthrough infections post-vaccination. In the post-vaccination era, IgM responses and those against nucleoprotein were much less prevalent. In previously infected individuals, vaccination boosted the immune response and there was a slight but statistically significant increase in responses after a 2nd compared to the 1st dose. Infected vaccinated participants had superior antibody levels across time compared to naïve-vaccinated people. mRNA vaccines and, particularly the Spikevax, induced higher antibodies after 1st and 2nd doses compared to Vaxzevria or Janssen COVID-19 vaccines. In multivariable regression analyses, antibody responses after vaccination were predicted by the type of vaccine, infection age, sex, smoking, and mental and cardiovascular diseases. CONCLUSIONS: Our data support that infected people would benefit from vaccination. Results also indicate that hybrid immunity results in superior antibody responses and infection-naïve people would need a booster dose earlier than previously infected people. Mental diseases are associated with less efficient responses to vaccination.

5.
British Journal of Haematology ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-2029286

ABSTRACT

Summary Administration of plasma therapy may contribute to viral control and survival of COVID‐19 patients receiving B‐cell‐depleting agents that impair humoral immunity. However, little is known on the impact of anti‐CD20 pre‐exposition on the kinetics of SARS‐CoV‐2‐specific antibodies. Here, we evaluated the relationship between anti‐spike immunoglobulin G (IgG) kinetics and the clinical status or intra‐host viral evolution after plasma therapy in 36 eligible hospitalized COVID‐19 patients, pre‐exposed or not to B‐cell‐depleting treatments. The majority of anti‐CD20 pre‐exposed patients (14/17) showed progressive declines of anti‐spike IgG titres following plasma therapy, contrasting with the 4/19 patients who had not received B‐cell‐depleting agents (p = 0.0006). Patients with antibody decay also depicted prolonged clinical symptoms according to the World Health Organization (WHO) severity classification (p = 0.0267) and SARS‐CoV‐2 viral loads (p = 0.0032) before complete virus clearance. Moreover, they had higher mutation rates than patients able to mount an endogenous humoral response (p = 0.015), including three patients with one to four spike mutations, potentially associated with immune escape. No relevant differences were observed between patients treated with plasma from convalescent and/or mRNA‐vaccinated donors. Our study emphasizes the need for an individualized clinical care and follow‐up in the management of COVID‐19 patients with B‐cell lymphopenia. [ FROM AUTHOR] Copyright of British Journal of Haematology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

6.
Immunology ; 2022.
Article in English | Web of Science | ID: covidwho-2019334

ABSTRACT

We evaluated the kinetics of antibody responses to Two years into the COVID-19 pandemic and 1 year after the start of vaccination rollout, the world faced a peak of cases associated with the highly contagious Omicron variant of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) and nucleocapsid (N) antigens over five cross-sectional visits (January-November 2021), and the determinants of pre-booster immunoglobulin levels, in a prospective cohort of vaccinated primary health care workers in Catalonia, Spain. Antibodies against S antigens after a full primary vaccination course, mostly with BNT162b2, decreased steadily over time and were higher in pre-exposed (n = 247) than naive (n = 200) individuals, but seropositivity was maintained at 100% (100% IgG, 95.5% IgA, 30.6% IgM) up to 319 days after the first dose. Antibody binding to variants of concern was highly maintained for IgG compared to wild type but significantly reduced for IgA and IgM, particularly for Beta and Gamma. Factors significantly associated with longer-term antibodies included age, sex, occupation, smoking, adverse reaction to vaccination, levels of pre-vaccination SARS-CoV-2 antibodies, interval between disease onset and vaccination, hospitalization, oxygen supply, post COVID and symptomatology. Earlier morning vaccination hours were associated with higher IgG responses in pre-exposed participants. Symptomatic breakthroughs occurred in 9/447 (2.01%) individuals, all among naive (9/200, 4.5%) and generally boosted antibody responses. Additionally, an increase in IgA and/or IgM seropositivity to variants, and N seroconversion at later time points (6.54%), indicated asymptomatic breakthrough infections, even among pre-exposed. Seropositivity remained highly stable over almost a year after vaccination. However, gradually waning of anti-S IgGs that correlate with neutralizing activity, coupled to evidence of an increase in breakthrough infections during the Delta and Omicron predominance, provides a rationale for booster immunization.

7.
2022 International Conference Laser Optics, ICLO 2022 ; 2022.
Article in English | Scopus | ID: covidwho-2018850

ABSTRACT

To date, a dangerous infectious disease of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) has been a significant source of morbidity and high mortality worldwide. In this work, an optical label-free method is developed for measurements and characterization of kinetics of antibodies to SARS-CoV-2 in real time. A biomarker of COVID-19, namely, spike protein of SARS-CoV-2 antigen was used as a model antigen. The proposed method employs inexpensive and widely available consumables compatible with various chemical interfaces. It is promising for assessment the kinetics of humoral response to SARS-CoV-2 infection or postvaccination. © 2022 IEEE.

8.
Biochemistry ; 2022.
Article in English | Web of Science | ID: covidwho-2016509

ABSTRACT

Remdesivir is an adenosine analogue that has a cyano substitution in the C1' position of the ribosyl moiety and a modified base structure to stabilize the linkage of the base to the C1' atom with its strong electron-withdrawing cyano group. Within the replication-transcription complex (RTC) of SARS-CoV-2, the RNA-dependent RNA polymerase nsp12 selects remdesivir monophosphate (RMP) over adenosine monophosphate (AMP) for nucleotide incorporation but noticeably slows primer extension after the added RMP of the RNA duplex product is translocated by three base pairs. Cryo-EM structures have been determined for the RTC with RMP at the nucleotide-insertion (i) site or at the i + 1, i + 2, or i + 3 sites after product translocation to provide a structural basis for a delayed-inhibition mechanism by remdesivir. In this study, we applied molecular dynamics (MD) simulations to extend the resolution of structures to the measurable maximum that is intrinsically limited by MD properties of these complexes. Our MD simulations provide (i) a structural basis for nucleotide selectivity of the incoming substrates of remdesivir triphosphate over adenosine triphosphate and of ribonucleotide over deoxyribonucleotide, (ii) new detailed information on hydrogen atoms involved in H-bonding interactions between the enzyme and remdesivir, and (iii) direct information on the catalytically active complex that is not easily captured by experimental methods. Our improved resolution of interatomic interactions at the nucleotide-binding pocket between remedesivir and the polymerase could help to design a new class of anti-SARS-CoV-2 inhibitors.

9.
9th International Congress on Design and Modeling of Mechanical Systems, CMSM 2021 ; : 439-447, 2023.
Article in English | Scopus | ID: covidwho-2013980

ABSTRACT

To contribute to the fight versus the coronavirus disease 2019, great efforts have been made by scientists around the world to improve the performance of detection devices so that they can efficiently and quickly detect the virus responsible for this disease. In this context we performed a two-dimensional finite element simulation on the binding kinetics of SARS-CoV-2 S protein of a biosensor using the alternating current electrothermal (ACET) effect. The ACET flow can produce vortex patterns, thereby improving the transportation of the target analyte to the binding surface and thus enhancing the performance of the biosensor. The results showed that the detection time can be improved under the electrothermal effect. The effect of certain design parameters concerning the reaction surface, such as its length as well as its position on the top wall of the microchannel, on the biosensor efficiency were also presented. Results showed that the decrease in the length of the binding surface can lead to an increase in the rate of the binding reaction and therefore decrease the biosensor response time. Also, moving the sensitive surface from an optimal position, which is opposite the electrodes, decreases the performance of the biosensor. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

10.
25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 ; : 1071-1072, 2021.
Article in English | Scopus | ID: covidwho-2012357

ABSTRACT

Here, we present a SARS-CoV-2 spike (S) protein lateral flow assay enhanced by electrokinetic focusing driven by ion concentration polarization (ICP). In this study, we optimize the configuration of membrane-modified electrodes for a stable location and greatest degree of enrichment for the plug of S-protein. We also show that a test line comprising bioconjugated beads further enhances enrichment. Using this system, we have achieved 40X enrichment of S-protein. We are currently evaluating the impact of increased dwell time over the test line. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

11.
25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 ; : 845-846, 2021.
Article in English | Scopus | ID: covidwho-2012345

ABSTRACT

We present fiber optic surface plasmon resonance (FO-SPR) label-free (LF) bioassays for quantification and kinetic profiling of complete antibody isotypes against the receptor binding domain (RBD) of SARS-CoV-2 spike protein. This was accomplished not only in serum but also for the first time directly in whole blood of COVID-19 convalescent patients. The LF bioassay was correlated with the traditional FO-SPR sandwich bioassay, the latter also benchmarked with ELISA. Compared to other serological tests, our approach is superior in: (1) information about kinetics, (2) rapid insight into the amount of all antibody isotypes and (3) exceptional compatibility with whole blood samples. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

12.
25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 ; : 127-128, 2021.
Article in English | Scopus | ID: covidwho-2011604

ABSTRACT

We will present a microfluidic assay to detect SARS-CoV-2 RNA from nasopharyngeal swab samples. Our method leverages isotachophoresis (ITP) to integrate sample preparation, RT-LAMP, and CRISPR-based nucleic acid detection in an automatable chip. For the first time, we use ITP to purify, pre-concentrate and isothermally amplify target nucleic acids into a ~1 µL reaction volume on-chip. The device then transitions LAMP amplicons into an on-chip zone containing Cas12-gRNA complexes and reporter molecules to measure target-activated CRISPR activity. We will use our method to automatically detect COVID-19 from nasopharyngeal swab samples. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

13.
Clinical journal of the American Society of Nephrology : CJASN ; 2022.
Article in English | MEDLINE | ID: covidwho-2009810

ABSTRACT

Kidney replacement therapy (KRT) is a vital, supportive treatment for patients with critical illness and severe AKI. The optimal timing, dose, and modality of KRT have been studied extensively, but gaps in knowledge remain. With respect to modalities, continuous KRT and intermittent hemodialysis are well-established options, but prolonged intermittent KRT is becoming more prevalent worldwide, particularly in emerging countries. Compared with continuous KRT, prolonged intermittent KRT offers similar hemodynamic stability and overall cost savings, and its intermittent nature allows patients time off therapy for mobilization and procedures. When compared with intermittent hemodialysis, prolonged intermittent KRT offers more hemodynamic stability, particularly in patients who remain highly vulnerable to hypotension from aggressive ultrafiltration over a shorter duration of treatment. The prescription of prolonged intermittent KRT can be tailored to patients' progression in their recovery from critical illness, and the frequency, flow rates, and duration of treatment can be modified to avert hemodynamic instability during de-escalation of care. Dosing of prolonged intermittent KRT can be extrapolated from urea kinetics used to calculate clearance for continuous KRT and intermittent hemodialysis. Practice variations across institutions with respect to terminology, prescription, and dosing of prolonged intermittent KRT create significant challenges, especially in creating specific drug dosing recommendations during prolonged intermittent KRT. During the coronavirus disease 2019 pandemic, prolonged intermittent KRT was rapidly implemented to meet the KRT demands during patient surges in some of the medical centers overwhelmed by sheer volume of patients with AKI. Ideally, implementation of prolonged intermittent KRT at any institution should be conducted in a timely manner, with judicious planning and collaboration among nephrology, critical care, dialysis and intensive care nursing, and pharmacy leadership. Future analyses and clinical trials with respect to prescription and delivery of prolonged intermittent KRT and clinical outcomes will help to guide standardization of practice.

14.
The American surgeon ; : 31348221124327, 2022.
Article in English | MEDLINE | ID: covidwho-2009259

ABSTRACT

BACKGROUND: Thomboelastography (TEG) is a point of care viscoelastic test that provides an assessment of clot formation and kinetics. Antiplatelet agents are commonly used but there is limited literature evaluating their possible effects on overall clot kinetics. We aimed to evaluate the relationship between antiplatelet agents and clot kinetics as defined by TEG. METHODS: This is a retrospective study of adult patients who underwent TEG from February 2018 to July 2020. Patients who received anticoagulants or blood transfusions within 72 hours, had an incomplete TEG, were diagnosed with COVID-19, or had liver failure were excluded. Patients were stratified based on antiplatelet status. RESULTS: Of 1060 patients, 119 were included (50 controls, 69 antiplatelet agents-37 aspirin monotherapy, 26 dual antiplatelet therapy). Between the control and antiplatelet therapy groups, there was no significant difference in clot time, maximal clot strength, or fibrinogen level. When compared to control patients, patients on dual antiplatelets had significantly higher fibrinogen levels (408.1 mg/dL vs 481.5 mg/dL, P = .013) but no significant differences in clot time or maximal clot strength. In our subgroup analysis, patients on dual antiplatelets had increased maximal clot strength (58.8° vs 63°, P = .005) and fibrinogen levels (384.1 mg/dL vs 481.5 mg/dL, P = .005) compared to those on aspirin alone. DISCUSSION: Compared to control patients and those on aspirin alone, patients on dual antiplatelets have increased maximal clot strength and increased fibrinogen levels. These results can help physicians better target product resuscitation in patients who are on antiplatelet agents.

15.
Annals of the Rheumatic Diseases ; 81:115-116, 2022.
Article in English | EMBASE | ID: covidwho-2008916

ABSTRACT

Background: Patients on immunomodulatory treatments mount an attenuated immune response following mRNA COVID-19 vaccination, yet longterm studies of vaccine-induced anti-SARS-CoV-2 antibody (Ab) kinetics are missing. Objectives: In this prospective observational study, we mapped the humoral antibody response to mRNA COVID-19 vaccines up to 24 weeks post full vaccination in patients with infammatory rheumatic diseases (IRDs). We aimed to assess differences due to treatment, age, past SARS-CoV-2 infection, and vaccine (BNT162b2 vs. mRNA-1273). Methods: Adult patients from the SCQM cohort who assented to an mRNA COVID-19 vaccine were recruited between 3/21-9/21. Participants answered questionnaires via an app and received kits for the self-collection of capillary blood samples at baseline, 4, 12, and 24 weeks post full vaccination. Samples were tested for IgG Ab against the S1 domain of the SARS-CoV-2 spike protein (anti-S1-IgG) using the EUROIMMUN ELISA. To examine differences in Ab titres arising from the defned parameters, while accounting for inter-assay variability, mixed effects continuous outcome logistic regression models were applied at each timepoint. Results: Samples were obtained from 570 patients: 67% female, mean age 53 y (SD 12 y) with 37% RA, 36% axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARDs & no glucocorticoids;15%), csD-MARDs (10%), TNFi (48%), IL-1/6/17/23i (14%), JAKi (6%), rituximab (RTX;4%), or abatacept (ABA;2%) in mono/combination therapy at the frst vaccination. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. For any Ab threshold, the odds of having a higher Ab titre at 4, 12, and 24 weeks post full vaccination were 3.3-4 times higher with mRNA-1273 compared to BNT162b2 (Table 1, Figure 1). TNFi, JAKi, RTX, and ABA as monotherapy resulted in signifcantly lower Ab levels compared to no medication at almost all timepoints. In combination therapy, TNFi, IL-1/6/17/23i, RTX, and csDMARDs led to consistently lower Ab titres at all timepoints compared to respective monotherapy. Conclusion: Compared to no medication, some immunomodulatory therapies resulted in markedly lower Ab levels at all timepoints. In IRD patients, a past SARS-CoV-2 infection resulted in strikingly increased immunogenicity, as did mRNA-1273 compared to BNT162b2.

16.
Microbiology spectrum ; : e0237122, 2022.
Article in English | MEDLINE | ID: covidwho-2008768

ABSTRACT

Diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged since the beginning of the COVID-19 pandemic. We investigated the immunological and pathological peculiarity of the SARS-CoV-2 beta variant of concern (VoC) compared to the ancestral strain. Comparative analysis of phenotype and pathology revealed that the beta VoC induces slower disease progression and a prolonged presymptomatic period in the early stages of SARS-CoV-2 infection but ultimately causes sudden death in the late stages of infection in the K18-hACE2 mouse model. The beta VoC induced enhanced activation of CXCL1/2-CXCR2-NLRP3-IL-1β signal cascade accelerating neutrophil recruitment and lung pathology in beta variant-infected mice, as evidenced by multiple analyses of SARS-CoV-2-induced inflammatory cytokines and transcriptomes. CCL2 was one of the most highly secreted cytokines in the early stages of infection. Its blockade reduced virus-induced weight loss and delayed mortality. Our study provides a better understanding of the variant characteristics and need for treatment. IMPORTANCE Since the outbreak of COVID-19, diverse SARS-CoV-2 variants have been identified. These variants have different infectivity and transmissibility from the ancestral strains. However, underlying molecular mechanisms have not yet been fully elucidated. In our study, the beta variant showed distinct pathological conditions and cytokine release kinetics from an ancestral strain in a mouse model. It was associated with higher neutrophil recruitment by increased levels of CXCL1/2, CXCR2, and interleukin 1β (IL-1β) at a later stage of viral infection. Our study will provide a better understanding of SARS-CoV-2 pathogenesis.

17.
Journal of Public Health in Africa ; 13:10, 2022.
Article in English | EMBASE | ID: covidwho-2006920

ABSTRACT

Introduction/ Background: By August 2021, 6.2 million cases of COVID-19 have been reported in Africa, which has about 70% of the global burden of HIV. The purpose of this study was to assess SARS-CoV-2 viral load in people living with and without HIV. Methods: We screened 2174 ambulatory patients presenting at three primary healthcare facilities and enrolled 106 consenting individuals who tested positive for SARSCoV- 2 primarily during the second wave in Durban, South Africa. Participants were enrolled within three days of SARS-CoV-2 screening and were then followed up at day 7, 14 and 28, and at month 3 and 6 post screening visit. Data on SARS-CoV-2 Ct number, as well as laboratory parameters were collected blinded to HIV status. Results: All 106 participants presented with mild to moderate COVID-19. Thirty of 106 participants were HIV positive;26 (86.5%) were on ART, of which 21 (77.8%) were virally supressed. Their CD4+ T-cell count ranged from 286 to 843 with the median 500 cells/mm3. In the HIV infected cohort, longer viral shedding was associated with having a CD4+ T cell count <500 at enrolment (adjusted hazards ratio: 0.31, 95% confidence interval: 0.12-0.80, p=0.015). We observed no significant differences in the clinical presentation and disease outcomes of HIV infected and HIV uninfected COVID-19 patients. Impact: Considering the implications that prolonged viral shedding could have on emergence of new viral variants and global vaccination efforts, HIV patients failing therapy should be prioritized for current prevention measures. Conclusion: Presence of HIV co-infection did not result in worsened clinical presentation in this cohort. Of note, we identified HIV infection with CD4 counts <500 as a potential driver of prolonged SARS-CoV-2 viral shedding.

18.
Journal of Public Health in Africa ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2006766

ABSTRACT

The proceedings contain 98 papers. The topics discussed include: COVID-19 clinical presentation and SARS-CoV-2 viral kinetics in people living with HIV;estimation of shedding time in laboratory-confirmed COVID-19 cases in South Africa, 2020;temporal dynamics of SARS-COV-2 viral load and related antibodies in West African patients: the COVADIS cohort;establishing a national SARS-CoV-2 surveillance network across South Africa to support wastewater-based genomic and epidemiological monitoring of the COVID pandemic, 2020-2021;prevalence of anti-SARS-CoV-2 IgG antibodies among Kenyan blood donors between June and August 2021;SARS-CoV-2 antibody prevalence in Sierra Leone, March 2021: a cross-sectional, nationally representative, age-stratified serosurvey;first national household seroprevalence survey of SARS-CoV 2 antibodies in Tunisia, April 2021;and SARS-CoV-2 seroprevalence across six states of Nigeria, October 2020 and June 2021.

19.
Indian Journal of Critical Care Medicine ; 26:S52-S54, 2022.
Article in English | EMBASE | ID: covidwho-2006348

ABSTRACT

Aim and background: The prevalence of acute kidney injury (AKI) among COVID-19 patients admitted to ICU was 46%. There is a paucity of data on renal recovery in a cohort of patients with AKI. Since COVID-19 is considered a public health issue, the estimates from this study might help in prognostication and health resource management. Objective: To evaluate the predictors and dynamics of renal recovery in critically ill COVID-19 patients with AKI. To study the duration and magnitude of AKI, the proportion of patients dependent on dialysis at hospital discharge, and mortality among COVID-AKI patients. Materials and methods: A single-centre, observational study was conducted in a mixed adult ICU from March 1, 2020, to February 1, 2021. COVID-19 patients who presented with or developed AKI as per KDIGO criteria within 7 days of ICU admission were included. Baseline characteristics, hemodynamic parameters, and renal recovery kinetics were captured till the discharge of the patient. Patients were followed up till 90 days post-discharge. Logistic regression with best subset selection was performed with renal recovery as an outcome (recovery is defined as attaining AKI stage 0 by KDIGO definition or 33% reduction of serum creatine from baseline) and APACHE II, rapidity of onset and progression of AKI, the magnitude of AKI, inflammatory markers, comorbidities, and P/F ratios as predictor variables. There were no multicollinearities, influential observations. Penalized-likelihood criteria (AIC and BIC models) were applied and a model with the lowest AIC or BIC was considered as the best fit to predict nonrecovery from AKI. Results: 200 patients' data were analysed, of which 67 patients recovered from AKI. Of the 67 patients, 16, 9, and 10 patients had transient AKI (<48 hours), persistent AKI (2-7 days), and AKD (7-90 days), respectively. Dialysis was required for 136 patients. The average duration for recovery from AKI was 7.4 days. The best fit model with the lowest BIC that predicted nonrecovery from AKI were: the combination of APACHE II, day onset of AKI, and magnitude of AKI. Results of logistic regression showed admission APACHE II, day onset of AKI, and magnitude of AKI were statistically significant in predicting non-recovery from AKI [OR 1.1 (p < 0.001;95% CI 1.06-1.16), OR 1.6 (p = 0.001;1.24-2.24), and OR 2.9 (p < 0.001;2.03-4.36), respectively]. This model had sufficient discrimination with AUC 0.86 and was well calibrated [Hosmer-Lemeshow (HL) chi2, p = 0.06]. Overall mortality among COVID-AKI patients was 84%. Two patients were dependent on dialysis at hospital discharge. Upon follow-up of 31 survivors for 90 days, four deaths were recorded. Conclusion: In our study, a higher APACHE II score at admission, the longer time interval between admission to the onset of AKI and the higher magnitude of AKI during ICU stay predicted poor renal recovery. A significant proportion of our patients require dialysis support and this poses a challenge on hospital resources and financial burden to the family. We observed higher mortality among COVID-19 patients with AKI compared to those with AKI not associated with COVID-19.

20.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2005669

ABSTRACT

Background: Bispecific antibodies (bsAb) are a promising class of therapeutics in RRMM. While hypogammaglobinemia (HGG) is anticipated due to plasma cell depletion, there is a lack of information about the degree of secondary immunodeficiency and resultant infectious complications. We investigated the kinetics of HGG in patients with RRMM on bsAb therapy. Methods: We identified and followed 42 patients treated on early clinical trials of bsAb at our institution between 2019 and 2021. Serial immunoglobulin levels and infections were obtained from the start of therapy until last follow up or 3 months after study exit. Results: 49 treatment courses were included from 42 individual patients. All patients were triple class exposed with a median of 5 prior lines of therapy. The median age was 67 (44-85) years, with 49% females. African Americans accounted for 18% of patients. 96% of patients had at least one prior ASCT. 90% of patients received bsAb targeting BCMA including 7 patients who received more than one line of BCMA targeting therapies. At a median follow up 9.5 (0.9-28.6) months, 40.8% of patients remained on bsAb therapy. At the start of therapy, the median IgG, IgA, and IgM levels were 560 (44-9436), 15 (5-3886) and 6 (5-64) mg/dL, respectively and 50% of patients had severe HGG (≤400mg/dl). Serum IgG levels reached a nadir at 3 months while, IgA and IgM at 1 month, from the start of therapy. The median nadir levels of IgG were 159 (40-2996) mg/dL, while it was < 5 mg/dL for both IgA and IgM. IgG levels were below the detectable range (< 40 mg/dl) in 28% of patients at some point during therapy. IgA and IgM were also below the detectable range (< 5 mg/dl) in 50% and 60% of patients, respectively. At last follow-up, the median IgG levels were 444 (40-1860) mg/dL and IgA 5 (5-254) mg/dL and IgM 5 (5-44) mg/dL. Additionally, 38% of patients remained severely hypogammaglobinemic. 57% (24/42) of patients received IVIG supplements in the current series. About 71% of patients had at least one infectious event and the cumulative incidence of infections progressively increased with increasing duration of therapy with risk at 3, 6, 9 12, 15 months being 41%, 57%, 64%, 67% and 70%, respectively. Among these, 54% of infection were bacterial. Viral infection accounted for 41% of infections. A third of patients had new infectious events during the first 90 days following stopping bsAb treatment. 57% (8/14) of patients did not mount a response to the primary COVID19 immunization series. Among the five patients with repeat antibody titers after the booster dose, 50% were still not able to mount an antibody response. Conclusions: bsAb therapy in RRMM can be associated with profound and prolonged HGG. The cumulative risk of infection correlated with the degree of HGG and progressively increases with treatment and persisted months after being off therapy. Additionally, an impaired antibody response to the COVID-19 immunization series was also noted.

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