Variant Virus Infections Research Articles

Analysis of CT signs, radiomic features and clinical characteristics for delta variant COVID-19 patients with different vaccination status

ObjectiveTo explore the characteristics of peripheral blood, high resolution computed tomography (HRCT) imaging and the radiomics signature (RadScore) in patients infected with delta variant virus under different coronavirus disease (COVID-19) vaccination status.Methods123 patients with delta variant virus infection collected from November 1, 2021 to March 1, 2022 were analyzed retrospectively. According to COVID-19 vaccination Status, they were divided into three groups: Unvaccinated group, partially vaccinated group and full vaccination group. The peripheral blood, chest HRCT manifestations and RadScore of each group were analyzed and compared.ResultsThe mean lymphocyte count 1.22 ± 0.49 × 10^9/L, CT score 7.29 ± 3.48, RadScore 0.75 ± 0.63 in the unvaccinated group; The mean lymphocyte count 1.55 ± 0.70 × 10^9/L, CT score 5.27 ± 2.72, RadScore 1.03 ± 0.46 in the partially vaccinated group; The mean lymphocyte count 1.87 ± 0.70 × 10^9/L, CT score 3.59 ± 3.14, RadScore 1.23 ± 0.29 in the fully vaccinated group. There were significant differences in lymphocyte count, CT score and RadScore among the three groups (all p < 0.05); Compared with the other two groups, the lung lesions in the unvaccinated group were more involved in multiple lobes, of which 26 cases involved the whole lung.ConclusionsThrough the analysis of clinical features, pulmonary imaging features and radiomics, we confirmed the positive effect of COVID-19 vaccine on pulmonary inflammatory symptoms and lymphocyte count (immune system) during delta mutant infection.

Global Epidemiology of Human Infections With Variant Influenza Viruses, 1959-2021: A Descriptive Study.

Although human case numbers of variant influenza viruses have increased worldwide, the epidemiology of human cases and human-to-human transmissibility of different variant viruses remain uncertain. We used descriptive statistics to summarize the epidemiologic characteristics of variant virus infections. The hospitalization rate, case-fatality, and hospitalization-fatality risks were used to assess disease severity. Transmissibility of variant viruses between humans was determined by the effective reproductive number (Re) and probability of infection following exposure to human cases. We identified 707 naturally infected cases of variant viruses from 1959 to 2021, and their spatiotemporal/demographic characteristics changed across subtypes. The clinical severity of cases of variant viruses was generally mild; patients older than 18 years with underlying conditions were associated with hospitalization. Of 69 clusters of human infections with variant viruses (median cluster size: 2), the upper limit of Re was 0.09 (H1N1v, H1N2v, and H3N2v: 0.20 vs 0.18 vs 0.05), whereas it was not significantly different from the pooled estimates for avian influenza A(H7N9) and A(H5N1) viruses (0.10). Moreover, contacts of H5N1 cases (15.7%) had a significantly higher probability of infection than contacts of individuals with H7N9 (4.2%) and variant virus infections (4.2%-7.2%). The epidemiology of cases of variant viruses varied across time periods, geographical regions, and subtypes during 1959-2021. The transmissibility of different variant viruses between humans remains limited. However, given the continuous evolution of viruses and the rapidly evolving epidemiology of cases of variant viruses, improving the surveillance systems for human variant virus infections is needed worldwide.

Do animal exhibitors support and follow recommendations to prevent transmission of variant influenza at agricultural fairs? A survey of animal exhibitor households after a variant influenza virus outbreak in Michigan.

SummaryInfluenza A viruses circulate in swine and can spread rapidly among swine when housed in close proximity, such as at agricultural fairs. Youth who have close and prolonged contact with influenza-infected swine at agricultural fairs may be at increased risk of acquiring influenza virus infection from swine. Animal and human health officials have issued written measures to minimize influenza transmission at agricultural exhibitions; however, there is little information on the knowledge, attitudes, and practice (KAP) of these measures among animal exhibitors. After an August 2016 outbreak of influenza A(H3N2) variant (“H3N2v”) virus infections (i.e., humans infected with swine influenza viruses) in Michigan, we surveyed households of animal exhibitors at eight fairs (including one with known H3N2v infections) to assess their KAP related to variant virus infections and their support for prevention measures. Among 170 households interviewed, most (90%, 151/167) perceived their risk of acquiring influenza from swine to be low or very low. Animal exhibitor households reported high levels of behaviours that put them at increased risk of variant influenza virus infections, including eating or drinking in swine barns (43%, 66/154) and hugging, kissing or snuggling with swine at agricultural fairs (31%, 48/157). Among several recommendations, including limiting the duration of swine exhibits and restricting eating and drinking in the animal barns, the only recommendation supported by a majority of households was the presence of prominent hand-washing stations with a person to monitor hand-washing behaviour (76%, 129/170). This is a unique study of KAP among animal exhibitors and highlights that animal exhibitor households engage in behaviours that could increase their risk of variant virus infections and have low support for currently recommended measures to minimize infection transmission. Further efforts are needed to understand the lack of support for recommended measures and to encourage healthy behaviours at fairs.

Outbreak of Influenza A(H3N2) Variant Virus Infections Among Persons Attending Agricultural Fairs Housing Infected Swine in Michigan and Ohio, July–August 2016

Outbreak of Influenza A(H3N2) Variant Virus Infections Among Persons Attending Agricultural Fairs Housing Infected Swine in Michigan and Ohio, July–August 2016

Outbreak of Influenza A(H3N2) Variant Virus Infections Among Persons Attending Agricultural Fairs Housing Infected Swine - Michigan and Ohio, July-August 2016.

On August 3, 2016, the Ohio Department of Health Laboratory reported to CDC that a respiratory specimen collected on July 28 from a male aged 13 years who attended an agricultural fair in Ohio during July 22-29, 2016, and subsequently developed a respiratory illness, tested positive by real-time reverse transcription-polymerase chain reaction (rRT-PCR) for influenza A(H3N2) variant* (H3N2v). The respiratory specimen was collected as part of routine influenza surveillance activities. The next day, CDC was notified of a child aged 9 years who was a swine exhibitor at an agricultural fair in Michigan who became ill on July 29, 2016, and tested positive for H3N2v virus at the Michigan Department of Health and Human Services Laboratory. Investigations by Michigan and Ohio health authorities identified 18 human infections linked to swine exhibits at agricultural fairs. To minimize transmission of influenza viruses from infected swine to visitors, agricultural fair organizers should consider prevention measures such as shortening the time swine are on the fairgrounds, isolating ill swine, maintaining a veterinarian on call, providing handwashing stations, and prohibiting food and beverages in animal barns. Persons at high risk for influenza-associated complications should be discouraged from entering swine barns.

Clinicopathological evaluation of intranasal, subcutaneous and intramuscular routes of vaccination against intratracheal challenge of Peste des petits ruminants virus in goats

An experiment was conducted to compare the efficacy of intranasal vaccination against caprine Peste des petits ruminant lineage 1 variant virus infection with intramuscular and subcutaneous vaccinations. Twenty four goats were divided into four equal groups. Group 1 was vaccinated intranasally, group 2 was vaccinated subcutaneously, and group 3 intramuscularly, while group 4 was the unvaccinated control. In each group, the vaccinations were carried out once. All goats were challenged intratracheally with PPR virus at a concentration of 106.5 TCID50 two weeks after vaccination and were euthanised 21 days after the challenge. The clinical, lung consolidation, gross and histopathological scores were employed using standard techniques. All data were analysed statistically using the paired t-test and one-way analysis of variance (ANOVA). Group 3 had the highest clinical score following the challenge of vaccinated group while deaths were observed only in group 4. Three goats in group 2 and 3 had pneumonic lung lesions, compared with none in group 1 and all the goats in group 4. The lung lesions in group 4 were significantly (P<0.05) severe than in others. Similarly, the lesions in group 2 and 3 were less severe with the right lung more affected (P>0.05) while group 1 had no consolidation. This study showed that PPR vaccination using subcutaneous, intramuscular and intranasal routes were protective but that of intranasal was found to be easy to apply hence it could be used for the prevention of the disease in small ruminants.

Viral Competition and Maternal Immunity Influence the Clinical Disease Caused by Very Virulent Infectious Bursal Disease Virus

The very virulent form of infectious bursal disease virus (vvIBDV) causes an immunosuppressive disease that is further characterized by the rapid onset of morbidity and high mortality in susceptible chickens. In 2009, vvIBDV was first reported in California, U. S. A., and since that time only a few cases of acute infectious bursal disease attributed to vvIBDV have been recognized in California. In other countries where vvIBDV has become established, it rapidly spreads to most poultry-producing regions. Two factors that may be involved in limiting the spread or reducing the severity of the clinical disease caused by vvIBDV in the U. S. A. are maternal immunity and competition with endemic variant strains of the virus. In this study, the ability of vvIBDV to infect and cause disease in maternally immune layer chickens was examined at weekly intervals over a 5-wk period during which their neutralizing maternal antibodies waned. Birds inoculated with vvIBDV at 2, 3, and 4 wk of age seemed healthy throughout the duration of the experiment, but macroscopic and microscopic lesions were observed in their bursa tissues. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay also confirmed the presence of vvIBDV RNA in their bursa tissues, indicating this virus was infecting the birds even at 2 wk of age when neutralizing maternal antibodies to infectious bursal disease virus were still relatively high (> 2000 geometric mean antibody titer). No mortality was observed in any birds when inoculated at 2, 3, or 4 wk of age; however, inoculation at 5 and 6 wk of age resulted in 10% and 20% mortality, respectively. Three experiments on the competition between vvIBDV and the two variant viruses T1 and FF6 were conducted. In all three experiments, specific-pathogen-free (SPF) birds that were inoculated with only the vvIBDV became acutely moribund, and except for Experiment 1 (62% mortality) all succumbed to the infection within 4 days of being exposed. When the variant viruses were inoculated into SPF chickens at 4 wk of age and the vvIBDV was administered 10 days later, a real-time reverse transcriptase (RT)-PCR assay was positive for the variant T1 and FF6 viral RNA but negative for vvIBDV RNA, indicating the vvIBDV isolate could not establish an infection in the bursa tissues of these birds. No clinical disease or mortality was observed in the birds, but macroscopic and microscopic lesions typical of a variant virus infection were observed. When the interval was shortened to 2 days, both variant viruses and vvIBDV were detected by RT-PCR, but the vvIBDV viral load in the bursa tissue was significantly lower compared with that of birds inoculated with vvIBDV alone. No clinical disease or mortality was observed, and macroscopic and microscopic lesions in the bursa of these birds were not typical of a vvIBDV infection but instead resembled a pathogenic classic virus infection. When the variant viruses and vvIBDV were inoculated simultaneously into 4-wk-old SPF chickens only the vvIBDV RNA was detected in the bursa tissues of the birds, and no reduction in viral load as measured by real-time RT-PCR was detected. Mortality (30%-40%) was reduced in these duel-infected birds compared with the 100% mortality observed in birds that received vvIBDV alone. The data suggest that maternal immunity and competition with variant viruses are acting to reduce the clinical signs and anticipated mortality after an vvIBDV infection, which may increase the chances that vvIBDV is not being recognized in commercial poultry operations.

Innate sensors of influenza virus: clues to developing better intranasal vaccines

Mucosal immunity acquired by natural infection with influenza viruses at the respiratory tract is more effective and cross-protective against subsequent variant virus infection than systemic immunity induced by parenteral immunization with inactivated vaccines. To develop an effective influenza vaccine, it is beneficial to mimic the process of natural infection that bridges innate and adaptive immune systems. The innate immune system that recognizes influenza virus infection consists of several classes of pattern-recognition receptors, including the Toll-like receptors, the retinoic acid-inducible gene-I-like receptors and the NOD-like receptors. Here, we review our current understanding of the mechanism of innate recognition of influenza and how the signals emanating from the innate sensors control adaptive immunity. Further, we discuss the potential roles of these receptors in developing intranasal influenza vaccines.

Naive Precursor Frequencies and MHC Binding Rather Than the Degree of Epitope Diversity Shape CD8+ T Cell Immunodominance

The primary CD8(+) T cell response of C57BL/6J mice against the 28 known epitopes of lymphocytic choriomeningitis virus (LCMV) is associated with a clear immunodominance hierarchy whose mechanism has yet to be defined. To evaluate the role of epitope competition in immunodominance, we manipulated the number of CD8(+) T cell epitopes that could be recognized during LCMV infection. Decreasing epitope numbers, using a viral variant lacking dominant epitopes or C57BL/6J mice lacking H-2K(b), resulted in minor response increases for the remaining epitopes and no new epitopes being recognized. Increasing epitope numbers by using F(1) hybrid mice, delivery by recombinant vaccinia virus, or epitope delivery as a pool in IFA maintained the overall response pattern; however, changes in the hierarchy did become apparent. MHC binding affinity of these epitopes was measured and was found to not strictly predict the hierarchy since in several cases similarly high binding affinities were associated with differences in immunodominance. In these instances the naive CD8(+) T cell precursor frequency, directly measured by tetramer staining, correlated with the response hierarchy seen after LCMV infection. Finally, we investigated an escape mutant of the dominant GP33-41 epitope that elicited a weak response following LCMV variant virus infection. Strikingly, dominance loss likely reflects a substantial reduction in frequencies of naive precursors specific for this epitope. Thus, our results indicate that an intrinsic property of the epitope (MHC binding affinity) and an intrinsic property of the host (naive precursor frequency) jointly dictate the immunodominance hierarchy of CD8(+) T cell responses.

Protection against influenza virus infection in polymeric Ig receptor knockout mice immunized intranasally with adjuvant-combined vaccines.

The role of secretory IgA in conferring cross-protective immunity was examined in polymeric (p)IgR knockout (KO) mice immunized intranasally with different inactivated vaccines prepared from A/PR/8/34 (H1N1), A/Yamagata/120/86 (H1N1), A/Beijing/262/95 (H1N1), and B/Ibaraki/2/85 viruses and infected with the A/PR/8/34 virus in the upper respiratory tract (RT)-restricting volume. In wild-type mice, immunization with A/PR/8/34 or its variant (A/Yamagata/120/86 and A/Beijing/262/95) vaccines conferred complete protection or partial cross-protection against infection, while the B-type virus vaccine failed to provide protection. The protection or cross-protection was accompanied by an increase in the nasal A/PR/8/34 hemagglutinin-reactive IgA concentration, which was estimated to be >30 times the serum IgA concentration and much higher than the nasal IgG concentration. In contrast, the blockade of transepithelial transport of dimeric IgA in pIgR-KO mice reduced the degree of protection or cross-protection, in parallel with the marked increase in serum IgA concentration and the decrease in nasal IgA concentration (about 20 and 0.3 times those in wild-type mice, respectively). The degree of the reduction of protection or cross-protection was moderately reversed by the low but non-negligible level of nasal IgA, transudates from the accumulated serum IgA. These results, together with the absence of the IgA-dependent cross-protection in the lower RT and the unaltered level of nasal or serum IgG in wild-type and pIgR-KO mice, confirm that the actively secreted IgA plays an important role in cross-protection against variant virus infection in the upper RT, which cannot be substituted by serum IgG.

経鼻インフルエンザウイルス蛋白質（あるいはプラスミドＤＮＡ）ワクチンの開発に伴う問題点

Natural influenza virus infection has been shown to be superior to current viral protein vaccines, which are administered subcutaneously to induce serum antiviral IgG antibodies (Abs), for inducing cross-protection against variant virus infection. The cross-protection induced by natural infection seems to be largely due to the induction of cross-reacting IgA Abs in the upper respiratory tract. This fact suggests that the development of immunization procedures to stimulate mucosal IgA production would improve the protective efficacy of viral DNA vaccines, as well as protein vaccines. To stimulate the IgA production, the protein vaccine together with cholera toxin or Escherichia coli heat-labile enterotoxin as an adjuvant were administered intranasally into BALB/c mice. The vaccination provided cross-protection against variant viruses, in parallel with the production of cross-reacting IgA Abs. Next, field trials were conducted to evaluate the efficacy of the nasal vaccine. The adjuvant-combined vaccine could induce both IgA and IgG responses higher than do the vaccine alone, with the prevention of influenza. Although no serious adverse effects were observed in the human trials, further studies will be required to reduce the toxicity and the allergenicity of these toxin adjuvant. New non-proteinous adjuvants, which may be better than the toxin adjuvant, remain to be developed. To develop effective DNA vaccines, plasmid DNAs encoding hemagglutinin (HA), neuraminidase (NA). matrix protein, nucleoprotein and nonstructural protein from the virus were immunized in mice by particle-mediated DNA transfer to the epidermis (gene gun).The viral surface glycoprotein (HA and NA)-expressing DNAs were most protective among the five DNAs. However, the DNA vaccine failed to provide cross-protection against variant viruses without inducing IgA Abs. Thus, the protective efficacy of the DNA vaccine would be improved by the DNA transfer to the mucosal epithelial cells, whose procedure remains to be developed.