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1.
Nat Med ; 28(7): 1501-1508, 2022 07.
Article in English | MEDLINE | ID: covidwho-1900517

ABSTRACT

In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient's body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.


Subject(s)
COVID-19 , Graft vs Host Disease , Humans , Mutation/genetics , SARS-CoV-2/genetics
2.
Open Forum Infect Dis ; 9(4): ofac089, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1769337

ABSTRACT

Background: Little is known about vaccine efficacy and sustainability among people with HIV (PWH). We estimated humoral and cellular immune responses postvaccination with BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine among PWH in Tel-Aviv Medical Center. Methods: The vaccine humoral response was evaluated by measuring immunoglobulin G (IgG) titers of antispike receptor-binding domain antibodies (anti-RBD IgG). Cellular response was assessed by stimulating donor peripheral blood mononuclear cells with pooled complete S-peptide mix. Results: One hundred thirty-six PWH who completed 2 doses of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine were tested for anti-RBD IgG and compared with 61 vaccinated health care workers (HCWs). The antibody titers were similar between the groups (median, 118 BAU/mL for PWH and 101.4 BAU/mL for HCWs; P = .231), although the mean time from second vaccine was 4.5 months in PWH and 6.7 months in HCWs (P < .0001). Longer time from second vaccine dose was associated with decreased antibody level, as were CD4 counts <300 cells/µL compared with higher CD4 counts (25.1 BAU/mL vs 119.3 BAU/mL, respectively; P = .047). There was no difference in cellular immune response between vaccinated PWH, convalescent unvaccinated PWH, and vaccinated HCWs. Conclusions: The humoral immune response of PWH was comparable to that of HCWs after BNT162b2 mRNA vaccination. Cellular immune response did not differ between vaccinated PWH, convalescent PWH, and vaccinated HCWs. PWH with CD4 counts <300 cells/µL (n = 9) had lower antibody titers compared with patients with counts >300 cells/µL (n = 127).

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329186

ABSTRACT

In some immunocompromised patients with chronic SARS-CoV-2 infection, dramatic adaptive evolution occurs, with substitutions reminiscent of those in variants of concern (VOCs). Here, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of twenty-seven chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations, yet a subset of mutations associated with successful global transmission was absent from chronic infections. The emergence of these mutations might dictate when variants from chronic infections can dramatically spread onwards. Next, we tested the ability to predict antibody-evasion mutations from patient- and viral-specific features, and found that viral rebound is strongly associated with the emergence of antibody-evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody-evasion in particular niches in a patient's body. We suggest that a trade-off exists between antibody-evasion and transmissibility that potentially constrains VOC emergence, and that monitoring chronic infections may be a means to predict future VOCs.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319390

ABSTRACT

Background: A high Neutrophil to Lymphocyte Ratio (NLR) is considered an unfavorable prognostic factor in various diseases, including COVID-19. The prognostic value of NLR in other respiratory viral infections, such as Influenza, has not hitherto been extensively studied. We aimed to compare the prognostic value of NLR in COVID-19, Influenza and Respiratory Syncytial Virus infection (RSV). Method: A retrospective cohort of COVID-19, Influenza and RSV patients admitted to the Tel Aviv Medical Center from January 2010 to October 2020 was analyzed. Laboratory, demographic, and clinical parameters were collected. Two way analyses of variance (ANOVA) was used to compare the association between NLR values and poor outcomes among the three groups. ROC curve analyses for each virus was applied to test the discrimination ability of NLR. Results: : 722 COVID-19, 2213 influenza and 482 RSV patients were included. Above the age of 50, NLR at admission was significantly lower among COVID-19 patients (P<0.001). NLR was associated with poor clinical outcome only in the COVID-19 group. ROC curve analysis was performed;the area under curve of poor outcomes for COVID-19 was 0.643, compared with 0.497 and 0.537 for Influenza and RSV respectively. In the COVID-19 group, multivariate logistic regression identified a high NLR (defined as a value above 4.7) to be a prognostic factor for poor clinical outcome, after adjusting for age, sex and Charlson comorbidity score (odds ratio of 1.6, P=0.005). Conclusions: : NLR at admission is lower and has more prognostic value in COVID-19 patients, when compared to Influenza and RSV.

5.
J Med Virol ; 2021 Nov 09.
Article in English | MEDLINE | ID: covidwho-1508794

ABSTRACT

Immunocompromised patients have an increased risk of persistent COVID-19 disease. We report here the clinical course of two patients with hematologic malignancies hospitalized due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In both patients, viral evolution including new spike gene mutations that occurred following treatment with anti-SARS-CoV-2 antibodies preparations, including convalescent plasma and bamlanivimab. These cases demonstrate the possibility of antibody-resistant SARS-CoV-2 infections evolution in immunocompromised patients.

6.
Sci Rep ; 11(1): 21519, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500511

ABSTRACT

A high neutrophil to lymphocyte ratio (NLR) is considered an unfavorable prognostic factor in various diseases, including COVID-19. The prognostic value of NLR in other respiratory viral infections, such as Influenza, has not hitherto been extensively studied. We aimed to compare the prognostic value of NLR in COVID-19, Influenza and Respiratory Syncytial Virus infection (RSV). A retrospective cohort of COVID-19, Influenza and RSV patients admitted to the Tel Aviv Medical Center from January 2010 to October 2020 was analyzed. Laboratory, demographic, and clinical parameters were collected. Two way analyses of variance (ANOVA) was used to compare the association between NLR values and poor outcomes among the three groups. ROC curve analyses for each virus was applied to test the discrimination ability of NLR. 722 COVID-19, 2213 influenza and 482 RSV patients were included. Above the age of 50, NLR at admission was significantly lower among COVID-19 patients (P < 0.001). NLR was associated with poor clinical outcome only in the COVID-19 group. ROC curve analysis was performed; the area under curve of poor outcomes for COVID-19 was 0.68, compared with 0.57 and 0.58 for Influenza and RSV respectively. In the COVID-19 group, multivariate logistic regression identified a high NLR (defined as a value above 6.82) to be a prognostic factor for poor clinical outcome, after adjusting for age, sex and Charlson comorbidity score (odds ratio of 2.9, P < 0.001). NLR at admission is lower and has more prognostic value in COVID-19 patients, when compared to Influenza and RSV.


Subject(s)
COVID-19/pathology , Influenza, Human/pathology , Respiratory Syncytial Virus Infections/pathology , Adult , Aged , Aged, 80 and over , Area Under Curve , COVID-19/immunology , COVID-19/virology , Female , Humans , Influenza, Human/immunology , Lymphocytes/cytology , Lymphocytes/metabolism , Male , Middle Aged , Neutrophils/cytology , Neutrophils/metabolism , Prognosis , ROC Curve , Respiratory Syncytial Virus Infections/immunology , Retrospective Studies , SARS-CoV-2/isolation & purification
7.
Infect Control Hosp Epidemiol ; : 1-4, 2021 Sep 20.
Article in English | MEDLINE | ID: covidwho-1442669

ABSTRACT

Real-world studies have demonstrated impressive effectiveness of the BNT162b2 COVID-19 vaccine in preventing symptomatic and asymptomatic SARS-CoV-2 infection. We describe an outbreak of SARS-CoV-2 infections in a hospital with high vaccine uptake. We found a low secondary attack rate (7%), suggesting low infectivity of vaccinated persons with vaccine breakthrough SARS-CoV-2 infections.

8.
PLoS One ; 16(8): e0255691, 2021.
Article in English | MEDLINE | ID: covidwho-1344159

ABSTRACT

Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is clinically essential, and is required also to monitor confirmed cases aiming to prevent further spread. Positive real-time PCR results at late time points following initial diagnosis may be clinically misleading as this methodology cannot account for the infection capabilities and the existence of whole genome sequences. In this study, 47 serial respiratory samples were tested by Allplex-nCoV test (Seegene), a triplex of three assays targeting the SARS-CoV-2 RdRP, E and N genes and subsequently assessed by next generation sequencing (NGS). COVID19 patients were tested at an early stage of the disease, when all these viral gene targets were positive, and at an advanced stage, when only the N gene target was positive in the Allplex-nCoV test. The corresponding NGS results showed the presence of complete viral genome copies at both early and advanced stages of the disease, although the total number of mapped sequences was lower in samples from advanced disease stages. We conclude that reduced viral transmission at this late disease stage may result from the low quantities of complete viral sequences and not solely from transcription favoring the N gene.


Subject(s)
COVID-19/genetics , SARS-CoV-2/genetics , Whole Genome Sequencing/methods , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , Female , Genome, Viral/genetics , High-Throughput Nucleotide Sequencing/methods , Humans , Male , Middle Aged , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/pathogenicity
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