ABSTRACT
Background: Though vaccines have been reported as highly efficacious in preventing severe COVID-19 disease, there is emerging data of severe infections, albeit a small number, in vaccinated individuals. We have conducted a retrospective observational study to assess the clinical characteristics, immunological response, and disease outcomes among the vaccinated and unvaccinated patients admitted to the ICU with severe COVID-19 disease. Methods: Study Design and Participants. We conducted a retrospective observational study in COVID ICU of a tertiary care hospital. Data were collected from the month of 1 April 2021 to 31 November 2021. All adult patients admitted to the ICU having severe COVID-19 disease were included in the study. Data were collected from the medical records database which included demographics, a clinical course in the ICU, laboratory and radiological parameters, and disease outcomes. In a subset of patients, cell-mediated immunity and S1S2-neutralising antibody assessment was done. Results: A total of 419 patients with severe COVID-19 were included in the study. Of the 419 patients, 90 (21.5%) were vaccinated, and 329 (78.5%) were unvaccinated. There was a significantly higher mortality in unvaccinated severe COVID 19 patients as compared to vaccinated severe COVID patients (46.2% vs 34.4%; P < 0.0455). The neutralizing antibody titre was significantly higher in survivors as compared to nonsurvivors (2139.8, SE ± 713.3 vs 471, SE ± 154.4); P < 0.026. Conclusion: Our study suggests the association of lower neutralizing antibody levels with mortality in ICU patients admitted with COVID-19 breakthrough infections.
ABSTRACT
Background Though vaccines have been reported as highly efficacious in preventing severe COVID-19 disease, there is emerging data of severe infections, albeit a small number, in vaccinated individuals. We have conducted a retrospective observational study to assess the clinical characteristics, immunological response, and disease outcomes among the vaccinated and unvaccinated patients admitted to the ICU with severe COVID-19 disease. Methods Study Design and Participants. We conducted a retrospective observational study in COVID ICU of a tertiary care hospital. Data were collected from the month of 1 April 2021 to 31 November 2021. All adult patients admitted to the ICU having severe COVID-19 disease were included in the study. Data were collected from the medical records database which included demographics, a clinical course in the ICU, laboratory and radiological parameters, and disease outcomes. In a subset of patients, cell-mediated immunity and S1S2-neutralising antibody assessment was done. Results A total of 419 patients with severe COVID-19 were included in the study. Of the 419 patients, 90 (21.5%) were vaccinated, and 329 (78.5%) were unvaccinated. There was a significantly higher mortality in unvaccinated severe COVID 19 patients as compared to vaccinated severe COVID patients (46.2% vs 34.4%;P < 0.0455). The neutralizing antibody titre was significantly higher in survivors as compared to nonsurvivors (2139.8, SE ± 713.3 vs 471, SE ± 154.4);P < 0.026. Conclusion Our study suggests the association of lower neutralizing antibody levels with mortality in ICU patients admitted with COVID-19 breakthrough infections.
ABSTRACT
Despite effective vaccination programs, waning immunity in the vaccinated populations and the emergence of variants of concern posed a risk of breakthrough infections. A booster dose was demonstrated to provide substantially increased protection against symptomatic disease and hospitalization. We aimed to evaluate immune memory and the efficacy of reducing the rate of SARS-CoV-2 infection post heterologous booster with CORBEVAX after primary vaccination with two doses of COVISHIELD. SARS-CoV-2 S1/S2 spike IgG and RBD-specific antibody responses were elicited with both booster vaccines, with a greater response in individuals receiving heterologous booster. T and B memory responses were increased with booster dose, whereas B memory needed a longer duration to develop in individuals who received a homologous booster (90 days) in comparison to a heterologous booster (30 days). RBD-specific B memory and antibody-secreting (non-memory) B lymphocytes were enhanced with both boosters; however, the duration of response was longer with the heterologous booster compared to the homologous, indicating greater protection with the heterologous booster. The rate of infection 14 days after administration of the heterologous booster was comparatively lower than that of the homologous booster, with the symptoms being much less or asymptomatic.
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 520 million people around the globe resulting in more than 6.2 million as of May 2022. Understanding the cell entry mechanism of SARS-CoV-2 and its entire repertoire is a high priority for developing improved therapeutics. The SARS-CoV-2 spike glycoprotein (S-protein) engages with host receptor ACE2 for adhesion and serine proteases furin and TMPRSS2 for proteolytic activation and subsequent entry. Recent studies have highlighted the molecular details of furin and S-protein interaction. However, the structural and molecular interplay between TMPRSS2 and S-protein remains enigmatic. Here, using biochemical, structural, computational, and molecular dynamics approaches, we investigated how TMPRSS2 recognizes and activates the S-protein to facilitate viral entry. First, we identified three potential TMPRSS2 cleavage sites in the S2 domain of S-protein (S2', T1, and T2) and reported the structure of TMPRSS2 with its individual catalytic triad. By employing computational modeling and structural analyses, we modeled the macromolecular structure of TMPRSS2 in complex with S-protein, which incited the mechanism of S-protein processing or cleavage for a new path of viral entry. On the basis of structure-guided drug screening, we also report the potential TMPRSS2 inhibitors and their structural interaction in blocking TMPRSS2 activity, which could impede the interaction with the spike protein. These findings reveal the role of TMPRSS2 in the activation of SARS-CoV-2 for its entry and insight into possible intervention strategies.
ABSTRACT
Emerging variants of SARS-CoV-2 with increased transmissibility or immune escape have been causing large outbreaks of COVID-19 infections across the world. As most of the vaccines currently in use have been derived from viral strains circulating in the early part of the pandemic, it becomes imperative to constantly assess the efficacy of these vaccines against emerging variants. In this hospital-based cohort study, we analysed clinical profiles and outcomes of 1161 COVID-19 hospitalized patients (vaccinated with COVISHIELD (ChAdOx1) or COVAXIN (BBV-152), n = 495 and unvaccinated n = 666) in Hyderabad, India between April 24th and May 31st 2021. Viral genome sequencing revealed that >90% of patients in both groups were harbouring the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Vaccinated individuals showed higher neutralizing antibodies (545+-1256 AU/ml Vs 51.1+-296 AU/ml; p<0.001) and significantly decreased Ferritin (392.26+-448.4 ng/mL Vs 544.82+-641.41 ng/mL; p<0.001) and LDH (559.45+-324.05 U/L Vs 644.99+- 294.03 U/L; p<0.001), when compared to the unvaccinated group. Severity of the disease (3.2% Vs 7.2%; p=0.0039) and requirement of ventilatory support (2.8% Vs 5.9%; p=0.0154) were significantly low in the vaccinated group despite the fact that these individuals had significantly higher age and risk factors. The rate of mortality was about 50% lower (2/132=1.51%) in the completely vaccinated breakthrough infections although mortality in individuals who had received a single dose was similar to the unvaccinated group (9/269=3.35% vs 23/666= 3.45%). Our results demonstrate that both COVISHIELD and COVAXIN are effective in preventing disease severity and mortality against the Delta variant in completely vaccinated hospitalized patients.
Subject(s)
COVID-19ABSTRACT
Background: A considerable amount of evidence demonstrates the potential of saliva in the diagnosis of COVID-19. Our aim was to determine the sensitivity of saliva versus swabs collected by healthcare workers (HCWs) and patients themselves to assess whether saliva detection can be offered as a cost-effective, risk-free method of SARS-CoV-2 detection.Methods: This study was conducted in a hospital involving outpatients and hospitalized patients. A total of 3018 outpatients (asymptomatic: 2683, symptomatic: 335) were screened. Of these, 200 qRT-PCR-confirmed SARS-CoV-2-positive patients were recruited (81 asymptomatic, 119 symptomatic). In addition, 101 SARS-CoV-2-positive hospitalized patients with symptoms were also enrolled in the study. From outpatients, HCWs collected nasopharyngeal swabs (NPS), saliva were obtained. From inpatients, HCWs collected swabs, patient-collected swabs, and saliva were obtained. qRT-PCR was performed to detect SARS-CoV-2 by TAQPATH assay to determine the sensitivity of saliva detection. Sensitivity, specificity and positive/negative predictive values (PPV, NPV) of detecting SARS-CoV-2 were calculated using MedCalc.Results: Of 3018 outpatient swabs tested by qRT-PCR, 200 were positive (males: 140, females: 60; aged 37.85±12.76 years). Of these, saliva was positive in 128 (64%); 39 of 81 asymptomatic (47%),89 of 119 symptomatic patients (74.78%). Sensitivity of detection was 60.9% (55.4-66.3%, CI 95%), with a negative predictive value of 36%(32.9-39.2%, CI 95%).Among 101 hospitalized patients (males:65, females: 36; aged 53.43±15.58 years), with HCW collected NPS as comparator, sensitivity of saliva was 56.1% (47.5-64.5, CI 95%), specificity 63.5%(50.4-75.3, CI95%) with PPV of 77.2% and NPV of 39.6% and that of self-swab was 52.3%(44-60.5%, CI95%), specificity 56.6% (42.3-70.2%, CI95%) with PPV 77.2% and NPV29.7%. Comparison of positivity with the onset of symptoms revealed highest detection in saliva on day 3 after onset of symptoms. Additionally, only saliva was positive in 13 (12.8%) hospitalized patients.Conclusion: Our results demonstrate the use of saliva to detect SARS-COV-2 in symptomatic patients early after the onset of symptoms. Additionally, these results suggest that saliva may not be recommended as a screening tool at the community level due to the lower detection rate than that for swabs. Saliva testing in symptomatic patients whose nasopharyngeal swab does not detect SARS-CoV-2 reduces false negativity.
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2, a highly transmittable pathogen has infected over 3.8 million people around the globe. The spike glycoprotein of SARS-CoV-2 engages host ACE2 for adhesion, TMPRSS2 for activation and entry. With the aid of whole-exome sequencing, we report a variant rs12329760 in TMPRSS2 gene and its mutant V160M, which might impede viral entry. Furthermore, we identified TMPRSS2 cleavage sites in S2 domain of spike glycoprotein and report the structure of TMPRSS2 in complex with spike glycoprotein. We also report the structures of protease inhibitors in complex with TMPRSS2, which could hamper the interaction with spike protein. These findings advance our understanding on the role of TMPRSS2 and in the development of potential therapeutics.Competing Interest StatementThe authors have declared no competing interest.View Full Text