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1.
Clin Infect Dis ; 72(12): 2248-2249, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1821697
2.
J Virol ; 96(5): e0179121, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1799229

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal influenza viruses are cocirculating in the human population. However, only a few cases of viral coinfection with these two viruses have been documented in humans with some people having severe disease and others mild disease. To examine this phenomenon, ferrets were coinfected with SARS-CoV-2 and human seasonal influenza A viruses (IAVs; H1N1 or H3N2) and were compared to animals that received each virus alone. Ferrets were either immunologically naive to both viruses or vaccinated with the 2019 to 2020 split-inactivated influenza virus vaccine. Coinfected naive ferrets lost significantly more body weight than ferrets infected with each virus alone and had more severe inflammation in both the nose and lungs compared to that of ferrets that were single infected with each virus. Coinfected, naive animals had predominantly higher IAV titers than SARS-CoV-2 titers, and IAVs were efficiently transmitted by direct contact to the cohoused ferrets. Comparatively, SARS-CoV-2 failed to transmit to the ferrets that cohoused with coinfected ferrets by direct contact. Moreover, vaccination significantly reduced IAV titers and shortened the viral shedding but did not completely block direct contact transmission of the influenza virus. Notably, vaccination significantly ameliorated influenza-associated disease by protecting vaccinated animals from severe morbidity after IAV single infection or IAV and SARS-CoV-2 coinfection, suggesting that seasonal influenza virus vaccination is pivotal to prevent severe disease induced by IAV and SARS-CoV-2 coinfection during the COVID-19 pandemic. IMPORTANCE Influenza A viruses cause severe morbidity and mortality during each influenza virus season. The emergence of SARS-CoV-2 infection in the human population offers the opportunity to potential coinfections of both viruses. The development of useful animal models to assess the pathogenesis, transmission, and viral evolution of these viruses as they coinfect a host is of critical importance for the development of vaccines and therapeutics. The ability to prevent the most severe effects of viral coinfections can be studied using effect coinfection ferret models described in this report.


Subject(s)
Antibodies, Viral/blood , COVID-19/prevention & control , Coinfection/prevention & control , Influenza Vaccines/immunology , Orthomyxoviridae Infections/prevention & control , Animals , COVID-19/immunology , Female , Ferrets/immunology , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/immunology , Orthomyxoviridae Infections/immunology , Vaccination , Virus Shedding
3.
Influenza Other Respir Viruses ; 16(3): 542-551, 2022 May.
Article in English | MEDLINE | ID: covidwho-1784668

ABSTRACT

BACKGROUND: Zanamivir is a neuraminidase inhibitor effective against influenza A and B viruses. In 2009, GlaxoSmithKline (GSK) began clinical development of intravenous (IV) zanamivir and initiated a global Compassionate Use Program (CUP) in response to the evolving H1N1 global pandemic. The goal of the CUP was to provide zanamivir to critically ill patients with limited treatment options. METHODS: Zanamivir was administered to patients with suspected or confirmed influenza infection who were not suitable for other approved antiviral treatments. Reporting of serious adverse events (SAEs) was mandatory and recorded in the GSK safety database. A master summary tracking sheet captured requests and patient characteristics. A case report form was available for detailing medical conditions, dosing, treatment duration, and clinical outcomes. RESULTS: In total, 4,033 requests were made for zanamivir treatment of hospitalized patients from 38 countries between 2009 and 2019; ≥95% patients received zanamivir via the IV route. Europe had the highest number of requests (n = 3,051) followed by North America (n = 713). At least 20 patients were aged ≤6 months, of whom 12 were born prematurely. The GSK safety database included 466 patients with ≥1 SAE, of whom 374 (80%) had a fatal outcome. Drug-related SAEs were reported in 41 (11%) patients, including hepatic failure (n = 6 [2%]) and acute kidney injury (n = 5 [1%)]. CONCLUSIONS: The CUP facilitated global access to zanamivir prior to product approval. No new safety concerns were identified in the CUP compared with IV zanamivir clinical studies.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Antiviral Agents/adverse effects , Compassionate Use Trials , Enzyme Inhibitors/adverse effects , Humans , Infant , Influenza, Human/drug therapy , Neuraminidase , Oseltamivir/therapeutic use , Zanamivir/adverse effects
5.
Sci Rep ; 12(1): 5867, 2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1778626

ABSTRACT

SARS-CoV-2 pandemic first emerged in late 2019 in China. It has since infected more than 298 million individuals and caused over 5 million deaths globally. The identification of essential proteins in a protein-protein interaction network (PPIN) is not only crucial in understanding the process of cellular life but also useful in drug discovery. There are many centrality measures to detect influential nodes in complex networks. Since SARS-CoV-2 and (H1N1) influenza PPINs pose 553 common human proteins. Analyzing influential proteins and comparing these networks together can be an effective step in helping biologists for drug-target prediction. We used 21 centrality measures on SARS-CoV-2 and (H1N1) influenza PPINs to identify essential proteins. We applied principal component analysis and unsupervised machine learning methods to reveal the most informative measures. Appealingly, some measures had a high level of contribution in comparison to others in both PPINs, namely Decay, Residual closeness, Markov, Degree, closeness (Latora), Barycenter, Closeness (Freeman), and Lin centralities. We also investigated some graph theory-based properties like the power law, exponential distribution, and robustness. Both PPINs tended to properties of scale-free networks that expose their nature of heterogeneity. Dimensionality reduction and unsupervised learning methods were so effective to uncover appropriate centrality measures.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza, Human , Humans , Influenza A Virus, H1N1 Subtype/metabolism , Protein Interaction Maps , Proteins/metabolism , SARS-CoV-2
6.
BMC Infect Dis ; 22(1): 331, 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1775315

ABSTRACT

BACKGROUND: A range of strict nonpharmaceutical interventions (NPIs) were implemented in many countries to combat the coronavirus 2019 (COVID-19) pandemic. These NPIs may also be effective at controlling seasonal influenza virus infections, as influenza viruses have the same transmission path as severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate the effects of different NPIs on the control of seasonal influenza. METHODS: Data for 14 NPIs implemented in 33 countries and the corresponding influenza virological surveillance data were collected. The influenza suppression index was calculated as the difference between the influenza positivity rate during its period of decline from 2019 to 2020 and during the influenza epidemic seasons in the previous 9 years. A machine learning model was developed using an extreme gradient boosting tree regressor to fit the NPI and influenza suppression index data. The SHapley Additive exPlanations tool was used to characterize the NPIs that suppressed the transmission of influenza. RESULTS: Of all NPIs tested, gathering limitations had the greatest contribution (37.60%) to suppressing influenza transmission during the 2019-2020 influenza season. The three most effective NPIs were gathering limitations, international travel restrictions, and school closures. For these three NPIs, their intensity threshold required to generate an effect were restrictions on the size of gatherings less than 1000 people, ban of travel to all regions or total border closures, and closing only some categories of schools, respectively. There was a strong positive interaction effect between mask-wearing requirements and gathering limitations, whereas merely implementing a mask-wearing requirement, and not other NPIs, diluted the effectiveness of mask-wearing requirements at suppressing influenza transmission. CONCLUSIONS: Gathering limitations, ban of travel to all regions or total border closures, and closing some levels of schools were found to be the most effective NPIs at suppressing influenza transmission. It is recommended that the mask-wearing requirement be combined with gathering limitations and other NPIs. Our findings could facilitate the precise control of future influenza epidemics and other potential pandemics.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza, Human , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Pandemics/prevention & control , Seasons
7.
Nat Commun ; 13(1): 1721, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1773976

ABSTRACT

Annual epidemics of seasonal influenza cause hundreds of thousands of deaths, high levels of morbidity, and substantial economic loss. Yet, global influenza circulation has been heavily suppressed by public health measures and travel restrictions since the onset of the COVID-19 pandemic. Notably, the influenza B/Yamagata lineage has not been conclusively detected since April 2020, and A(H3N2), A(H1N1), and B/Victoria viruses have since circulated with considerably less genetic diversity. Travel restrictions have largely confined regional outbreaks of A(H3N2) to South and Southeast Asia, B/Victoria to China, and A(H1N1) to West Africa. Seasonal influenza transmission lineages continue to perish globally, except in these select hotspots, which will likely seed future epidemics. Waning population immunity and sporadic case detection will further challenge influenza vaccine strain selection and epidemic control. We offer a perspective on the potential short- and long-term evolutionary dynamics of seasonal influenza and discuss potential consequences and mitigation strategies as global travel gradually returns to pre-pandemic levels.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , COVID-19/epidemiology , Humans , Influenza A Virus, H3N2 Subtype , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Pandemics/prevention & control , Seasons
8.
PLoS One ; 17(3): e0266456, 2022.
Article in English | MEDLINE | ID: covidwho-1770772

ABSTRACT

The world health organization estimates that more than a quarter of the human population is infected with parasitic worms that are called helminths. Many helminths suppress the immune system of their hosts to prolong their survival. This helminth-induced immunosuppression "spills over" to unrelated antigens and can suppress the immune response to vaccination against other pathogens. Indeed, several human studies have reported a negative correlation between helminth infections and responses to vaccinations. Using mice that are infected with the parasitic nematode Litomosoides sigmodontis as a model for chronic human filarial infections, we reported previously that concurrent helminth infection impaired the vaccination-induced protection against the human pathogenic 2009 pandemic H1N1 influenza A virus (2009 pH1N1). Vaccinated, helminth-infected mice produced less neutralizing, influenza-specific antibodies than vaccinated naïve control mice. Consequently helminth-infected and vaccinated mice were not protected against a challenge infection with influenza virus but displayed high virus burden in the lung and a transient weight loss. In the current study we tried to improve the vaccination efficacy using vaccines that are licensed for humans. We either introduced a prime-boost vaccination regimen using the non-adjuvanted anti-influenza vaccine Begripal or employed the adjuvanted influenza vaccine Fluad. Although both strategies elevated the production of influenza-specific antibodies and protected mice from the transient weight loss that is caused by an influenza challenge infection, sterile immunity was not achieved. Helminth-infected vaccinated mice still had high virus burden in the lung while non-helminth-infected vaccinated mice rapidly cleared the virus. In summary we demonstrate that basic improvements of influenza vaccination regimen are not sufficient to confer sterile immunity on the background of helminth-induced immunosuppression, despite amelioration of pathology i.e. weight loss. Our findings highlight the risk of failed vaccinations in helminth-endemic areas, especially in light of the ongoing vaccination campaign to control the COVID-19 pandemic.


Subject(s)
COVID-19 , Helminthiasis , Helminths , Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Adjuvants, Immunologic , Animals , Antibodies, Viral , Humans , Influenza, Human/complications , Influenza, Human/prevention & control , Mice , Pandemics , Vaccination , Weight Loss
10.
J Epidemiol Glob Health ; 11(4): 413-425, 2021 12.
Article in English | MEDLINE | ID: covidwho-1766934

ABSTRACT

The expansion and standardization of clinical trials, as well as the use of sensitive and specific molecular diagnostics methods, provide new information on the age-specific roles of influenza and other respiratory viruses in development of severe acute respiratory infections (SARI). Here, we present the results of the multicenter hospital-based study aimed to detect age-specific impact of influenza and other respiratory viruses (ORV). The 2018-2019 influenza season in Russia was characterized by co-circulation of influenza A(H1N1)pdm09 and A(H3N2) virus subtypes which were detected among hospitalized patients with SARI in 19.3% and 16.4%, respectively. RSV dominated among ORV (15.1% of total cases and 26.8% in infants aged ≤ 2 years). The most significant SARI agents in intensive care units were RSV and influenza A(H1N1)pdm09 virus, (37.3% and 25.4%, respectively, of PCR-positive cases). Hyperthermia was the most frequently registered symptom for influenza cases. In contrast, hypoxia, decreased blood O2 concentration, and dyspnea were registered more often in RSV, rhinovirus, and metapneumovirus infection in young children. Influenza vaccine effectiveness (IVE) against hospitalization of patients with PCR-confirmed influenza was evaluated using test-negative case-control design. IVE for children and adults was estimated to be 57.0% and 62.0%, respectively. Subtype specific IVE was higher against influenza A(H1N1)pdm09, compared to influenza A(H3N2) (60.3% and 45.8%, respectively). This correlates with delayed antigenic drift of the influenza A(H1N1)pdm09 virus and genetic heterogeneity of the influenza A(H3N2) population. These studies demonstrate the need to improve seasonal influenza prevention and control in all countries as states by the WHO Global Influenza Strategy for 2019-2030 initiative.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Respiratory Tract Infections , Adult , Age Factors , Child , Child, Preschool , Hospitalization , Humans , Infant , Influenza A Virus, H3N2 Subtype , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Seasons
11.
Sci Rep ; 12(1): 5247, 2022 03 28.
Article in English | MEDLINE | ID: covidwho-1764199

ABSTRACT

The clothes laundering process affords numerous opportunities for dissemination of infectious virus from contaminated clothing to appliance surfaces and other household surfaces and eventually to launderer's hands. We have explored the efficacy of laundry sanitizers for inactivating coronaviruses and influenza viruses. Virucidal efficacy was tested using standardized suspension inactivation methods (EN 14476) or hard-surface inactivation methods (ASTM E1053-20) against SARS-CoV-2, human coronavirus 229E (HCoV 229E), influenza A virus (2009-H1N1 A/Mexico), or influenza B virus (B/Hong Kong). Efficacy was measured in terms of log10 reduction in infectious virus titer, after 15 min contact time (suspension studies) or 5 min contact time (hard surface studies) at 20 ± 1 °C. In liquid suspension studies, laundry sanitizers containing p-chloro-m-xylenol (PCMX) or quaternary ammonium compounds (QAC) caused complete inactivation (≥ 4 log10) of HCoV 229E and SARS-CoV-2 within 15 min contact time at 20 ± 1 °C. In hard surface studies, complete inactivation (≥ 4 log10) of each coronavirus or influenza virus, including SARS-CoV-2, was observed following a 5-min contact time at 20 ± 1 °C. Respiratory viruses may remain infectious on clothing/fabrics and environmental surfaces for hours to days. The use of a laundry sanitizer containing microbicidal actives may afford mitigation of the risk of contamination of surfaces during handling of the laundry and washing appliances (i.e., washer/dryer or basin), adjacent surfaces, the waste water stream, and the hands of individuals handling clothes contaminated with SARS-CoV-2, influenza viruses, or other emerging enveloped viruses.


Subject(s)
COVID-19 , Coronavirus 229E, Human , Influenza A Virus, H1N1 Subtype , Influenza A virus , COVID-19/prevention & control , Humans , SARS-CoV-2
12.
MEDICC Rev ; 24(1): 9-13, 2022 Jan 31.
Article in English | MEDLINE | ID: covidwho-1761728

ABSTRACT

As 2021 drew to a close, Cuba struggled to contain the highly transmissible omicron variant of SARS-CoV-2, braced for a new wave of infections and kept a close eye on other variants of concern popping up around the world-a common experience to countries everywhere as we head into the second year of the pandemic. In Cuba, however, there is one marked difference making all the difference: by early January, 87% of the population was fully vaccinated using a three-dose schedule of vaccines developed and produced on the island.[1] This massive vaccination campaign is complemented by a rapid booster rollout-also using Cuban vaccines-that began in December 2021 and was ongoing as we finalized this issue. The island nation was able to achieve the third highest COVID-19 vaccination rate in the world[2] after decades of scientific investment, research, discovery and innovation; regulatory oversight and compliance; professional training; and increased production capacity. But a vaccine is only as effective as the health system charged with administering it-in a safe and timely manner, to as many people as possible. Here too, Cuba has decades of experience, including a national pediatric immunization program where 98% of children under 5 are immunized against 13 diseases,[3] an annual polio vaccination campaign (both launched in 1962 and uninterrupted since) and campaigns to contain epidemics such as H1N1. When the first COVID-19 cases were detected on the island in March 2020, Cuba harnessed this vaccine experience, making a hard tack towards developing its own vaccines. Two of the main protagonists in the country's biotechnology development, the Finlay Vaccine Institute (IFV) and the Genetic Engineering and Biotechnology Center (CIGB), both with several groundbreaking preventive and therapeutic vaccines in their portfolios, led the search for a vaccine. Today, Cuba has three vaccines authorized for emergency use-Soberana 02 and Soberana Plus developed by IFV, and Abdala, developed by CIGB. Schedules with these vaccines have demonstrated more than 90% efficacy in clinical trials,[4] and after regulatory approval for emergency use, became the backbone of Cuban COVID-19 vaccination efforts. A fourth vaccine, Mambisa (CIGB), administered nasally, and a fifth, Soberana 01 (IFV) are still in clinical trials. For this installment in MEDICC Review's series spotlighting leading women of Cuban science, we sat down with Dr Verena Muzio, Director of Clinical Research at CIGB. A pioneer of Cuba's biotechnology sector, she is an immunologist with a doctorate in biological sciences. Her professional trajectory began researching the genetically engineered hepatitis B surface antigen that led to the development of Cuba's recombinant hepatitis B vaccine in 1989. The same technological platform used in this vaccine was used to develop CIGB's Abdala vaccine against SARS-CoV-2-part of the reason Cuba was able to secure a vaccine so quickly. A phase 3 clinical trial determined a 92.28% efficacy rate for Abdala, with results to appear in forthcoming publications.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , COVID-19 Vaccines , Child , Cuba , Female , Humans , Pandemics , SARS-CoV-2 , Trust
13.
JNMA J Nepal Med Assoc ; 60(246): 214-217, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1761647

ABSTRACT

Influenza has a common occurrence during its peak seasons. It usually causes disease of the respiratory tract including severe acute respiratory distress syndrome. However, it may also cause disease and complication of other organ systems. We present a rare complication of influenza in which a patient secondary to influenza developed massive middle cerebral artery ischemic stroke. The patient however survived following recovery of both severe acute respiratory distress syndrome and ischemic stroke after decompressive craniectomy and a prolonged intensive care unit stay. This case report is to highlight the importance of influenza related complications besides the pulmonary infliction which can lead to morbidity and even mortality if not managed on time.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Ischemic Stroke , Respiratory Distress Syndrome , Humans , Influenza, Human/complications , Influenza, Human/diagnosis , Middle Cerebral Artery , Respiratory Distress Syndrome/etiology
14.
J Virol ; 96(6): e0187321, 2022 03 23.
Article in English | MEDLINE | ID: covidwho-1759293

ABSTRACT

Given the current coronavirus disease 2019 (COVID-19) pandemic, coinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) is a major concern for public health. However, the immunopathogenic events occurring with coinfections of SARS-CoV-2 and IAV remain unclear. Here, we report the pathogenic and immunological consequences of SARS-CoV-2 and IAV H1N1 coinfection in the K18-hACE2 transgenic mouse model. Compared with a single infection with SARS-CoV-2 or IAV, coinfections not only prolonged the primary virus infection period but also increased immune cell infiltration and inflammatory cytokine levels in bronchoalveolar lavage fluid leading to severe pneumonia and lung damage. Moreover, coinfections caused severe lymphopenia in peripheral blood, resulting in reduced total IgG, neutralizing antibody titers, and CD4+ T cell responses against each virus. This study sheds light on the immunopathogenesis of SARS-CoV-2 and IAV coinfection, which may guide the development of effective therapeutic strategies for the treatment of patients coinfected with these viruses. IMPORTANCE The cocirculation of influenza virus merging with the COVID-19 pandemic raises a potentially severe threat to public health. Recently, increasing numbers of SARS-CoV-2 and influenza virus coinfection have been reported from many countries. It is a worrisome issue that SARS-CoV-2 coinfection with other pathogens may worsen the clinical outcome and severity of COVID-19 and increase fatality. Here, we evaluated SARS-CoV-2 and IAV coinfection using the K18-hACE2 mouse model. Coinfected mice exhibited increased mortality with prolonged IAV shedding. Furthermore, coinfected mice showed a higher level of cytokines and chemokines than a single infection condition. Interestingly, our data show that coinfected mice showed significantly fewer virus-specific and neutralizing antibodies than the mice with a single infection. Overall, this study suggests that coinfection aggravates viral pathology by impaired neutralizing antibody response.


Subject(s)
COVID-19 , Coinfection , Influenza A Virus, H1N1 Subtype , Influenza A virus , Animals , Antibodies, Neutralizing , CD4-Positive T-Lymphocytes/pathology , Disease Models, Animal , Humans , Mice , Pandemics , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/pathology
15.
Arch Pathol Lab Med ; 146(4): 433-439, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1753892

ABSTRACT

CONTEXT.­: From the onset of the human immunodeficiency virus (HIV) pandemic in the 1980s to the recent coronavirus disease 2019 (COVID-19) pandemic, multiple viral pandemics have occurred and all have been associated with hematologic complications of varying severity. OBJECTIVE.­: To review the hematologic complications associated with the HIV and other viral pandemics, the current theories regarding their causation, and the incidence and clinical impact of these complications on infected patients. DATA SOURCES.­: Peer-reviewed medical literature and the author's personal experience. CONCLUSIONS.­: The HIV and other viral pandemics have been associated with a variety of hematologic complications that often cause significant morbidity and mortality in affected patients. HIV infection is associated with multiple hematologic disorders, many of which have a lower incidence in the era of highly active antiretroviral therapy but still represent a major clinical problem for HIV-infected patients. Our understanding of the pathogenesis of HIV-related hematologic complications, including HIV-associated lymphoproliferative disorders, has evolved in recent years. Other viral pandemics, including H1N1 influenza, severe acute respiratory syndrome (SARS) coronavirus, Middle East respiratory syndrome (MERS) coronavirus, and COVID-19, have also been associated with hematologic complications of varying severity. Our emerging understanding of the pathogenesis of the hematologic complications of HIV, COVID-19, and other viral pandemics may help in prevention, correct diagnosis, and treatment of these complications in current and future pandemics.


Subject(s)
COVID-19 , HIV Infections , Influenza A Virus, H1N1 Subtype , Middle East Respiratory Syndrome Coronavirus , COVID-19/complications , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , SARS-CoV-2
16.
Viruses ; 14(2)2022 02 21.
Article in English | MEDLINE | ID: covidwho-1744920

ABSTRACT

Involvement of macrophages in the SARS-CoV-2-associated cytokine storm, the excessive secretion of inflammatory/anti-viral factors leading to the acute respiratory distress syndrome (ARDS) in COVID-19 patients, is unclear. In this study, we sought to characterize the interplay between the virus and primary human monocyte-derived macrophages (MDM). MDM were stimulated with recombinant IFN-α and/or infected with either live or UV-inactivated SARS-CoV-2 or with two reassortant influenza viruses containing external genes from the H1N1 PR8 strain and heterologous internal genes from a highly pathogenic avian H5N1 or a low pathogenic human seasonal H1N1 strain. Virus replication was monitored by qRT-PCR for the E viral gene for SARS-CoV-2 or M gene for influenza and TCID50 or plaque assay, and cytokine levels were assessed semiquantitatively with qRT-PCR and a proteome cytokine array. We report that MDM are not susceptible to SARS-CoV-2 whereas both influenza viruses replicated in MDM, albeit abortively. We observed a modest cytokine response in SARS-CoV-2 exposed MDM with notable absence of IFN-ß induction, which was instead strongly induced by the influenza viruses. Pre-treatment of MDM with IFN-α enhanced proinflammatory cytokine expression upon exposure to virus. Together, the findings concur that the hyperinflammation observed in SARS-CoV-2 infection is not driven by macrophages.


Subject(s)
Inflammation/virology , Macrophages/immunology , Macrophages/virology , SARS-CoV-2/immunology , Virus Replication/genetics , Cell Line , Cell Line, Tumor , Cells, Cultured , Cytokines/analysis , Cytokines/immunology , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H5N1 Subtype/genetics , Influenza A Virus, H5N1 Subtype/immunology , Interferon-alpha/pharmacology , Macrophages/drug effects , Male , SARS-CoV-2/genetics , SARS-CoV-2/physiology
17.
BMJ Open ; 12(3): e051216, 2022 03 11.
Article in English | MEDLINE | ID: covidwho-1741624

ABSTRACT

INTRODUCTION: Sexual and Reproductive Health and Rights (SRHR) of young people continue to present a high burden and remain underinvested. This is more so in low and middle-income countries (LMICs), where empirical evidence reveals disruption of SRHR maintenance, need for enhancement of programmes, resources and services during pandemics. Despite the importance of the subject, there is no published review yet combining recent disease outbreaks such as (H1N1/09, Zika, Ebola and SARS-COV-2) to assess their impact on adolescents and youth SRHR in LMICs. METHODS AND ANALYSIS: We will adopt a four-step search to reach the maximum possible number of studies. In the first step, we will carry out a limitedpreliminary search in databases for getting relevant keywords (appendix 1). Second, we will search in four databases: Pubmed, Cochrane Library, Embase and PsycINFO. The search would begin from the inception of the first major outbreak in 2009 (H1N1/09) up to the date of publication of the protocol in early 2022. We will search databases using related keywords, screen title & abstract and review full texts of the selected titles to arrive at the list of eligible studies. In the third stage, we will check their eligibility to the included article's reference list. In the fourth stage, we will check the citations of included papers in phase 2 to complete our study selection. We will include all types of original studies and without any language restriction in our final synthesis. Our review results will be charted for each pandemic separately and include details pertaining to authors, year, country, region of the study, study design, participants (disaggregated by age and gender), purpose and report associated SRHR outcomes. The review will adhere to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guideline (PRISMA-ScR). PATIENT AND PUBLIC INVOLVEMENT: Patients or public were not involved in this study. ETHICS AND DISSEMINATION: Ethical assessment is not required for this study. The results of the study will be presented in peer-reviewed publications and conferences on adolescent SRHR.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Zika Virus Infection , Zika Virus , Adolescent , COVID-19/epidemiology , Developing Countries , Disease Outbreaks , Humans , Reproductive Health , SARS-CoV-2 , Systematic Reviews as Topic , Zika Virus Infection/epidemiology
18.
J Virol ; 96(7): e0010022, 2022 Apr 13.
Article in English | MEDLINE | ID: covidwho-1728835

ABSTRACT

Understanding how animal influenza A viruses (IAVs) acquire airborne transmissibility in humans and ferrets is needed to prepare for and respond to pandemics. Here, we investigated in ferrets the replication and transmission of swine H1N1 isolates P4 and G15, whose majority population had decreased polymerase activity and poor hemagglutinin (HA) stability, respectively. For both isolates, a minor variant was selected and transmitted in ferrets. Polymerase-enhancing variant PA-S321 airborne-transmitted and propagated in one ferret. HA-stabilizing variant HA1-S210 was selected in all G15-inoculated ferrets and was transmitted by contact and airborne routes. With an efficient polymerase and a stable HA, the purified minor variant G15-HA1-S210 had earlier and higher peak titers in inoculated ferrets and was recovered at a higher frequency after airborne transmission than P4 and G15. Overall, HA stabilization played a more prominent role than polymerase enhancement in the replication and transmission of these viruses in ferrets. The results suggest pandemic risk-assessment studies may benefit from deep sequencing to identify minor variants with human-adapted traits. IMPORTANCE Diverse IAVs circulate in animals, yet few acquire the viral traits needed to start a human pandemic. A stabilized HA and mammalian-adapted polymerase have been shown to promote the adaptation of IAVs to humans and ferrets (the gold-standard model for IAV replication, pathogenicity, and transmissibility). Here, we used swine IAV isolates of the gamma lineage as a model to investigate the importance of HA stability and polymerase activity in promoting replication and transmission in ferrets. These are emerging viruses that bind to both α-2,6- and α-2,3-linked receptors. Using isolates containing mixed populations, a stabilized HA was selected within days in inoculated ferrets. An enhanced polymerase was also selected and propagated after airborne transmission to a ferret. Thus, HA stabilization was a stricter requirement, yet both traits promoted transmissibility. Knowing the viral traits needed for pandemic potential, and the relative importance of each, will help identify emerging viruses of greatest concern.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza, Human , Orthomyxoviridae Infections , Animals , Ferrets , Hemagglutinin Glycoproteins, Influenza Virus , Hemagglutinins , Humans , Swine
19.
J Antibiot (Tokyo) ; 75(5): 258-267, 2022 May.
Article in English | MEDLINE | ID: covidwho-1728737

ABSTRACT

A series of lupane-, oleanane- and dammarane-based triterpenoids with 3ß-amino, A-ring azepano- and 3,4-seco-fragments has been synthesized and evaluated for antiviral activity against influenza A(H1N1) virus. It was found that azepanodipterocarpol 8 and 3ß-amino-28-oxoallobetulin 11 showed antiviral activity with IC50 1.1 and 2.6 µg ml-1, and selectivity index of 19 and 10, respectively.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Triterpenes , Antiviral Agents/pharmacology , Humans , Influenza, Human/drug therapy , Oleanolic Acid/analogs & derivatives , Triterpenes/pharmacology
20.
In Vivo ; 36(2): 954-960, 2022.
Article in English | MEDLINE | ID: covidwho-1732570

ABSTRACT

BACKGROUND/AIM: Multiple reports from all over the world link COVID-19 with endothelial/coagulation disorders as well as a dysregulated immune response. This study tested the hypothesis that immunostimulation will be greater in COVID-19 patients than in patients with H1N1 infection or bacterial sepsis. Also, whether an increase in immune stimulation will be accompanied by a more severely affected endothelium/coagulation system was examined. PATIENTS AND METHODS: Twenty-three septic patients, admitted in the Intensive Care Unit (ICU), were enrolled (9 with SARS-CoV-2, 5 with H1N1 pneumonia, 9 with bacterial sepsis). Myeloperoxidase (MPO) activity along with certain endothelial/coagulation factors were assessed on admission (time point 1) and at either improvement or deterioration (time point 2). RESULTS: MPO levels were significantly higher in COVID-19 patients compared to both other groups. Furthermore, in patients with COVID-19, vWF levels did not differ significantly, fVIII levels were lower while ADAMTS-13 activity was higher compared to patients with H1N1 pneumonia and bacterial sepsis (a trend in the latter). CONCLUSION: Increased immunostimulation was noted in COVID-19 patients compared to other septic patients; however, this was not accompanied by greater disturbance of the clotting system and/or more severe endothelial injury.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Influenza A Virus, H1N1 Subtype , Sepsis , Blood Coagulation Disorders/etiology , COVID-19/complications , Humans , Immunization , SARS-CoV-2 , Sepsis/complications
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