ABSTRACT
Background: In patients (pts) with hematological malignancies, COVID-19 is considered to be associated with a high risk of severe morbidity and mortality. While anti-COVID-19 vaccination of such pts has become the standard of care, pts undergoing lymphodepleting therapy fail to generate protective serological response due to either the nature of their underlying disease or exposure to therapy. Aims: This study aimed to assess serological response to vaccination with BNT162b2 (Pfizer) as well as COVID-19-related morbidity and mortality in Hodgkin lymphoma (HL) pts. Methods: The above vaccine was available in Israel from January 2021 and all pts with hematological malignancies were recommended to undergo vaccination with 2 doses of this vaccine, injected 21 days apart. Six months later a 3rd dose was recommended and in another 3 months a 4th dose was available for pts at risk. Serology tests were performed at least 2 weeks after the 2nd vaccination. The SARS-CoV-2 IgG II Quant (Abbott©) assay was used to measure levels of IgG antibodies (Abs) against the SARS-CoV-2 spike protein. A result was considered positive if the IgG level was ≥150 AU/ml, which was defined as an adequate serological response. Results: The current non-interventional single-center study evaluated the outcome of 55 HL pts (median age 46 years, 53% females);51% of pts had advanced HL. Study participants received 1-9 lines of therapy (median 1 line). Six pts had COVID-19 prior to vaccination, 49 were vaccinated: 9 with 2 doses, 36 with 3 doses and 4 with 4 doses of BNT162b2. Following initial 2 vaccine doses and after a 3rd dose Ab levels >150 AU/ml were developed in 85% and 89.5% of pts, respectively. At a median of 95 days post-2nd vaccination, Ab levels were 2024 (1-29400) and 4 (0-7539) in 48 patients with no background disease versus 7 pts treated with lymphodepleting drugs or having a background disease, respectively. During the follow-up, 5 vaccinated pts were diagnosed with COVID-19 when the Delta variant was prevalent and 9-during the Omicron wave. Notably, similar Ab levels were observed in those infected with Omicron and in non-infected pts, reflecting the genetic drift of this variant. A further analysis was performed to compare findings in a subgroup of 7 pts who had an additional background disease along with HL, such as chronic lymphocytic leukemia, s/p kidney transplantation, solid tumor, or those who were heavily pretreated, including therapy with bendamustine, versus the values observed in the rest 48 pts. The median age in the former subgroup was 58 (31-80) years, which was significantly older than in the remaining pts [median 45 (18-78) years] and median Ab levels were 4 (0-7539) AU/ml and 2024 (1-2940) AU/ml, respectively. Notably, after the 3rd vaccination, the median Ab level in both groups was 7000 AU/ml. Summary/Conclusion: The results of the current study show that at least 85% of HL pts develop a high titer of anti-spike antibodies after vaccination with 2 BNT162b2 doses. These titers substantially increased post the 3rd vaccine dose. Only a minority of HL pts who had additional background diseases or were heavily pretreated, failed to develop an adequate serological response;however, some of them had high Ab titers post-3rd and 4th vaccinations. In this study, morbidity and mortality rates of HL pts infected with COVID-19 were lower than those reported in pts with other lymphoma types.
ABSTRACT
A series of stringent non-pharmacological and pharmacological interventions were implemented to contain the pandemic but the pandemic continues. Moreover, vaccination breakthrough infection and reinfection in convalescent coronavirus disease 2019 (COVID-19) cases have been reported. Further, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerged with mutations in spike (S) gene, the target of most current vaccines. Importantly, the mutations exhibit a trend of immune escape from the vaccination. Herein the scientific question that if the vaccination drives genetic or antigenic drifts of SARS-CoV-2 remains elusive. We performed correlation analyses to uncover the impacts of wide vaccination on epidemiological characteristics of COVID-19. In addition, we investigated the evolutionary dynamics and genetic diversity of SARS-CoV-2 under immune pressure by utilizing the Bayesian phylodynamic inferences and the lineage entropy calculation respectively. We found that vaccination coverage was negatively related to the infections, severe cases, and deaths of COVID-19 respectively. With the increasing vaccination coverage, the lineage diversity of SARS-CoV-2 dampened, but the rapid mutation rates of the S gene were identified, and the vaccination could be one of the explanations for driving mutations in S gene. Moreover, new epidemics resurged in several countries with high vaccination coverage, questioning their current pandemic control strategies. Hence, integrated vaccination and non-pharmacological interventions are critical to control the pandemic. Furthermore, novel vaccine preparation should enhance its capabilities to curb both disease severity and infection possibility.
ABSTRACT
Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.
ABSTRACT
How many incoming travelers (I0 at time 0, equivalent to the 'founders' in evolutionary genetics) infected with SARS-CoV-2 who visit or return to a region could have started the epidemic of that region? I0 would be informative about the initiation and progression of epidemics. To obtain I0 , we analyze the genetic divergence among viral populations of different regions. By applying the 'individual-output' model of genetic drift to the SARS-CoV-2 diversities, we obtain I0 < 10, which could have been achieved by one infected traveler in a long-distance flight. The conclusion is robust regardless of the source population, the continuation of inputs (It for t > 0) or the fitness of the variants. With such a tiny trickle of human movement igniting many outbreaks, the crucial stage of repressing an epidemic in any region should, therefore, be the very first sign of local contagion when positive cases first become identifiable. The implications of the highly 'portable' epidemics, including their early evolution prior to any outbreak, are explored in the companion study (Ruan et al., personal communication).