Influenza Virus Survival Research Articles

The Impact of Heating, Ventilation, and Air-Conditioning Design Features on the Transmission of Viruses, Including SARS-CoV-2: Overview of Reviews.

The COVID-19 or SARS-CoV-2 outbreak was declared a pandemic by the World Health Organization in March 2020. Almost 2 years later (early February 2022), the World Health Organization reported over 383 million cases of the disease caused by the virus, with over 5.6 million deaths worldwide. Debate regarding the routes of transmission was substantial early in the pandemic; however, airborne transmission emerged as an important consideration. Infectious airborne agents can spread within the built environment through heating, ventilation, and air-conditioning (HVAC) systems. Multiple features of HVAC systems can influence transmission (eg, ventilation, filtration, UV radiation, and humidity). Understanding how HVAC features influence airborne transmission is critical to mitigate the spread of infectious agents. Given the airborne transmission of SARS-CoV-2, an overview of reviews was conducted to understand what is already known from the scientific literature about how virus transmission may be affected by HVAC design features in the built environment. Ovid MEDLINE and Compendex were searched from inception to January 2021. Two reviewers independently screened the titles, abstracts, and full text of potentially relevant reviews, using a priori inclusion criteria: systematic reviews examining the effects of HVAC design features on virus transmission. Two reviewers independently assessed the methodological quality using AMSTAR2. Searching identified 361 citations, of which 45 (12.5%) were potentially relevant and 7 (2%) were included. Reviews were published between 2007 and 2021 and included 47 virus studies. Two earlier reviews (2007 and 2016) of 21 studies found sufficient evidence that mechanical ventilation (airflow patterns and ventilation rates) plays a role in airborne transmission; however, both found insufficient evidence to quantify the minimum mechanical ventilation requirements. One review (2017) of 9 studies examining humidity and indoor air quality found that influenza virus survival was lowest between 40% and 80% relative humidity; the authors noted that ventilation rates were a confounding variable. Two reviews (2021) examined mitigation strategies for coronavirus transmission, finding that transmission decreased with increasing temperature and relative humidity. One review (2020) identified 14 studies examining coronavirus transmission in air-conditioning systems, finding that HVAC systems played a role in virus spread during previous coronavirus outbreaks. One review (2020) examined virus transmission interventions in public ground transportation, finding ventilation and filtration to be effective. Seven reviews synthesizing 47 studies demonstrated a role for HVAC in mitigating airborne virus transmission. Ventilation, humidity, temperature, and filtration can play a role in the viability and transmission of viruses, including coronaviruses. Recommendations for minimum standards were not possible owing to few studies investigating a given HVAC parameter. This overview examining HVAC design features and their effects on the airborne transmission of viruses serves as a starting point for future systematic reviews and identifying priorities for primary research.

Influenza Virus-Induced Novel miRNAs Regulate the STAT Pathway.

MicroRNAs (miRNAs) are essential regulators of gene expression in humans and can control pathogenesis and host–virus interactions. Notably, the role of specific host miRNAs during influenza virus infections are still ill-defined. The central goal of this study was to identify novel miRNAs and their target genes in response to influenza virus infections in airway epithelium. Human airway epithelial cells exposed to influenza A virus (IAV) induced several novel miRNAs that were identified using next-generation sequencing (NGS) and their target genes by biochemical methods. NGS analysis predicted forty-two RNA sequences as possible miRNAs based on computational algorithms. The expression patterns of these putative miRNAs were further confirmed using RT-PCR in human bronchial epithelial cells exposed to H1N1, H9N1(1P10), and H9N1 (1WF10) strains of influenza virus. A time-course study showed significant downregulation of put-miR-34 in H1N1 and put-miR-35 in H9N1(1P10)-infected cells, which is consistent with the NGS data. Additionally, put-miR-34 and put-miR-35 showed a high fold enrichment in an argonaute-immunoprecipitation assay compared to the controls, indicating their ability to form a complex with argonaute protein and RNA-induced silencing complex (RISC), which is a typical mode of action found with miRNAs. Our earlier studies have shown that the replication and survival of influenza virus is modulated by certain transcription factors such as NF-ĸB. To identify the target(s) of these putative miRNAs, we screened 84 transcription factors that have a role in viral pathogenesis. Cells transfected with mimic of the put-miR-34 showed a significant decrease in the expression of Signal Transducers and Activators of Transcription 3 (STAT3), whereas the inhibitor of put-miR-34 showed a significant increase in STAT3 expression and its phosphorylation. In addition, put-miR-34 had 76% homology to the untranslated region of STAT3. NGS and PCR array data submitted to the Gene Ontology project also predicted the role of transcription factors modulated by put-miR-34. Our data suggest that put-miR-34 may be a good target for antiviral therapy.

Sustainability of SARS-CoV-2 in aerosols: should we worry about airborne transmission?

Sustainability of SARS-CoV-2 in aerosols: should we worry about airborne transmission?

Coronavirus and Environmental Engineering Science

Coronavirus and Environmental Engineering Science

Characterising viable virus from air exhaled by H1N1 influenza-infected ferrets reveals the importance of haemagglutinin stability for airborne infectivity.

The transmissibility and pandemic potential of influenza viruses depends on their ability to efficiently replicate and be released from an infected host, retain viability as they pass through the environment, and then initiate infection in the next host. There is a significant gap in knowledge about viral properties that enable survival of influenza viruses between hosts, due to a lack of experimental methods to reliably isolate viable virus from the air. Using a novel technique, we isolate and characterise infectious virus from droplets emitted by 2009 pandemic H1N1-infected ferrets. We demonstrate that infectious virus is predominantly released early after infection. A virus containing a mutation destabilising the haemagglutinin (HA) surface protein displayed reduced survival in air. Infectious virus recovered from droplets exhaled by ferrets inoculated with this virus contained mutations that conferred restabilisation of HA, indicating the importance of influenza HA stability for between-host survival. Using this unique approach can improve knowledge about the determinants and mechanisms of influenza transmissibility and ultimately could be applied to studies of airborne virus exhaled from infected people.

The Influence of Simulated Sunlight on the Inactivation of Influenza Virus in Aerosols.

Environmental parameters, including sunlight levels, are known to affect the survival of many microorganisms in aerosols. However, the impact of sunlight on the survival of influenza virus in aerosols has not been previously quantified. The present study examined the influence of simulated sunlight on the survival of influenza virus in aerosols at both 20% and 70% relative humidity using an environmentally controlled rotating drum aerosol chamber. Measured decay rates were dependent on the level of simulated sunlight, but they were not significantly different between the 2 relative humidity levels tested. In darkness, the average decay constant was 0.02 ± 0.06 min-1, equivalent to a half-life of 31.6 minutes. However, at full intensity simulated sunlight, the mean decay constant was 0.29 ± 0.09 min-1, equivalent to a half-life of approximately 2.4 minutes. These results are consistent with epidemiological findings that sunlight levels are inversely correlated with influenza transmission, and they can be used to better understand the potential for the virus to spread under varied environmental conditions.

Mechanistic insights into the effect of humidity on airborne influenza virus survival, transmission and incidence.

Influenza incidence and seasonality, along with virus survival and transmission, appear to depend at least partly on humidity, and recent studies have suggested that absolute humidity (AH) is more important than relative humidity (RH) in modulating observed patterns. In this perspective article, we re-evaluate studies of influenza virus survival in aerosols, transmission in animal models and influenza incidence to show that the combination of temperature and RH is equally valid as AH as a predictor. Collinearity must be considered, as higher levels of AH are only possible at higher temperatures, where it is well established that virus decay is more rapid. In studies of incidence that employ meteorological data, outdoor AH may be serving as a proxy for indoor RH in temperate regions during the wintertime heating season. Finally, we present a mechanistic explanation based on droplet evaporation and its impact on droplet physics and chemistry for why RH is more likely than AH to modulate virus survival and transmission.

Humidity as a non-pharmaceutical intervention for influenza A

Influenza is a global problem infecting 5–10% of adults and 20–30% of children annually. Non-pharmaceutical interventions (NPIs) are attractive approaches to complement vaccination in the prevention and reduction of influenza. Strong cyclical reduction of absolute humidity has been associated with influenza outbreaks in temperate climates. This study tested the hypothesis that raising absolute humidity above seasonal lows would impact influenza virus survival and transmission in a key source of influenza virus distribution, a community school. Air samples and objects handled by students (e.g. blocks and markers) were collected from preschool classrooms. All samples were processed and PCR used to determine the presence of influenza virus and its amount. Additionally samples were tested for their ability to infect cells in cultures. We observed a significant reduction (p < 0.05) in the total number of influenza A virus positive samples (air and fomite) and viral genome copies upon humidification as compared to control rooms. This suggests the future potential of artificial humidification as a possible strategy to control influenza outbreaks in temperate climates. There were 2.3 times as many ILI cases in the control rooms compared to the humidified rooms, and whether there is a causal relationship, and its direction between the number of cases and levels of influenza virus in the rooms is not known. Additional research is required, but this is the first prospective study suggesting that exogenous humidification could serve as a scalable NPI for influenza or other viral outbreaks.

Avian influenza overview May - August 2018.

Between 16 May and 15 August 2018, three highly pathogenic avian influenza (HPAI) A(H5N8) outbreaks in poultry establishments and three HPAI A(H5N6) outbreaks in wild birds were reported in Europe. Three low pathogenic avian influenza (LPAI) outbreaks were reported in three Member States. Few HPAI and LPAI bird cases have been detected in this period of the year, in accordance with the seasonal expected pattern of LPAI and HPAI. There is no evidence to date that HPAI A(H5N8) and A(H5N6) viruses circulating in Europe have caused any human infections. The risk of zoonotic transmission to the general public in Europe is considered to be very low. Several HPAI outbreaks in poultry were reported during this period from Russia. The presence of the A(H5N2) and A(H5N8) viruses in parts of Russia connected with fall migration routes of wild birds is of concern for possible introduction and spread with wild birds migrating to the EU. Although few AI outbreaks were observed in Africa, Asia and the Middle East during the reporting period, the probability of AI virus introductions from non‐EU countries via wild birds particularly via the north‐eastern route from Russia is increasing, as the fall migration of wild birds will start in the coming weeks. Further, the lower temperatures in autumn and winter may facilitate the environmental survival of avian influenza viruses potentially introduced to Europe.

Survival of the Enveloped Virus Phi6 in Droplets as a Function of Relative Humidity, Absolute Humidity, and Temperature.

ABSTRACTInfectious diseases caused by enveloped viruses, such as influenza, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), cause thousands of deaths and billions of dollars of economic losses per year. Studies have found a relationship among temperature, humidity, and influenza virus incidence, transmission, or survival; however, there are contradictory claims about whether absolute humidity (AH) or relative humidity (RH) is most important in mediating virus infectivity. Using the enveloped bacteriophage Phi6, which has been suggested as a surrogate for influenza viruses and coronaviruses, we designed a study to discern whether AH, RH, or temperature is a better predictor of virus survival in droplets. Our results show that Phi6 survived best at high (>85%) and low (<60%) RHs, with a significant decrease in infectivity at mid-range RHs (∼60 to 85%). At an AH of less than 22 g · m−3, the loss in infectivity was less than 2 orders of magnitude; however, when the AH was greater than 22 g · m−3, the loss in infectivity was typically greater than 6 orders of magnitude. At a fixed RH of 75%, infectivity was very sensitive to temperature, decreasing two orders of magnitude between 19°C and 25°C. We used random forest modeling to identify the best environmental predictors for modulating virus infectivity. The model explained 83% of variation in Phi6 infectivity and suggested that RH is the most important factor in controlling virus infectivity in droplets. This research provides novel information about the complex interplay between temperature, humidity, and the survival of viruses in droplets.IMPORTANCE Enveloped viruses are responsible for a number of infectious diseases resulting in thousands of deaths and billions of dollars of economic losses per year in the United States. There has been a lively debate in the literature over whether absolute humidity (AH) or relative humidity (RH) modulates virus infectivity. We designed a controlled study and used advanced statistical modeling techniques specifically to address this question. By providing an improved understanding of the relationship between environmental conditions and virus infectivity, our work will ultimately lead to improved strategies for predicting and controlling disease transmission.

Indoor air humidity, air quality, and health - An overview.

There is a long-standing dispute about indoor air humidity and perceived indoor air quality (IAQ) and associated health effects. Complaints about sensory irritation in eyes and upper airways are generally among top-two symptoms together with the perception "dry air" in office environments. This calls for an integrated analysis of indoor air humidity and eye and airway health effects. This overview has reviewed the literature about the effects of extended exposure to low humidity on perceived IAQ, sensory irritation symptoms in eyes and airways, work performance, sleep quality, virus survival, and voice disruption. Elevation of the indoor air humidity may positively impact perceived IAQ, eye symptomatology, and possibly work performance in the office environment; however, mice inhalation studies do not show exacerbation of sensory irritation in the airways by low humidity. Elevated humidified indoor air appears to reduce nasal symptoms in patients suffering from obstructive apnea syndrome, while no clear improvement on voice production has been identified, except for those with vocal fatigue. Both low and high RH, and perhaps even better absolute humidity (water vapor), favors transmission and survival of influenza virus in many studies, but the relationship between temperature, humidity, and the virus and aerosol dynamics is complex, which in the end depends on the individual virus type and its physical/chemical properties. Dry and humid air perception continues to be reported in offices and in residential areas, despite the IAQ parameter "dry air" (or "wet/humid air") is semantically misleading, because a sensory organ for humidity is non-existing in humans. This IAQ parameter appears to reflect different perceptions among other odor, dustiness, and possibly exacerbated by desiccation effect of low air humidity. It is salient to distinguish between indoor air humidity (relative or absolute) near the breathing and ocular zone and phenomena caused by moisture-damage of the building construction and emissions therefrom. Further, residential versus public environments should be considered as separate entities with different characteristics and demands of humidity. Research is needed about particle, bacteria and virus dynamics indoors for improvement of quality of life and with more focus on the impact of absolute humidity. "Dry (or wet) air" should be redefined to become a meaningful IAQ descriptor.

Morphological and Biochemical Characteristics of Avian Faecal Droppings and Their Impact on Survival of Avian Influenza Virus.

Environmental specimens such as faecal droppings are considered important for the detection of avian influenza viruses (AIV). In view of lower rates of AIV isolation from avian faecal droppings, characterization of droppings is imperative to elucidate contributing factors. However, there are no reports on morphological and biochemical characteristics of droppings. The objective of the present study was the characterization of droppings from different avian species and their impact on the AIV detection and isolation. A total of 373 droppings belonging to 61 avian species from 22 families of apparently healthy wild migratory, resident, domestic birds and poultry were studied during five winter migratory bird seasons between 2007 to 2012 and 2016-2017. The colour, morphology and size of the droppings varied from species-to-species. These data could be useful for the identification of avian species. Droppings from 67% of the avian species showed acidic pH (4.5-6.5); nine species showed neutral pH (7.0), and 11 species showed alkaline pH (7.5). The infectious titers of AIV in droppings with acidic pH were significantly lower (p<0.05) than those of the droppings with neutral and alkaline pH. However, acidic pH did not hamper AIV detection by real-time RT-PCR. In order to avoid the impact of acidic pH, collecting fresh droppings into viral transport medium (pH 7.0-7.5) would help improve the rate of AIV isolation.

Influenza transmission during extreme indoor conditions in a low-resource tropical setting.

Influenza transmission occurs throughout the planet across wide-ranging environmental conditions. However, our understanding of the environmental factors mediating transmission is evaluated using outdoor environmental measurements, which may not be representative of the indoor conditions where influenza is transmitted. In this study, we examined the relationship between indoor environment and influenza transmission in a low-resource tropical population. We used a case-based ascertainment design to enroll 34 households with a suspected influenza case and then monitored households for influenza, while recording indoor temperature and humidity data in each household. We show that the indoor environment is not commensurate with outdoor conditions and that the relationship between indoor and outdoor conditions varies significantly across homes. We also show evidence of influenza transmission in extreme indoor environments. Specifically, our data suggests that indoor environments averaged 29°C, 18g/kg specific humidity, and 68% relative humidity across 15 transmission events observed. These indoor settings also exhibited significant temporal variability with temperatures as high as 39°C and specific and relative humidity increasing to 22g/kg and 85%, respectively, during some transmission events. However, we were unable to detect differences in the transmission efficiency by indoor temperature or humidity conditions. Overall, these results indicate that laboratory studies investigating influenza transmission and virus survival should increase the range of environmental conditions that they assess and that observational studies investigating the relationship between environment and influenza activity should use caution using outdoor environmental measurements since they can be imprecise estimates of the conditions that mediate transmission indoors.

Seasonal Influenza Epidemics and El Niños.

Seasonal influenza epidemics occur annually during the winter in the northern and southern hemispheres, but timing of peaks and severity vary seasonally. Low humidity, which enhances survival and transmission of influenza virus, is the major risk factor. Both El Niño and La Niña phases of El Niño-southern oscillation (ENSO), which determine inter-annual variation of precipitation, are putative risk factors. This study was done to determine if seasonality, timing of peak, and severity of influenza epidemics are coupled to phases of ENSO. Monthly time series of positive specimens for influenza viruses and of multivariate El Niño-Southern Oscillation Index from January 2000 to August 2015 were analyzed. Seasonality, wavelet spectra, and cross-wavelet spectra analyses were performed. Of 31 countries in the dataset, 21 were in the northern hemisphere and 10 in the southern hemisphere. The highest number of influenza cases occurred in January in the northern hemisphere, but in July in the southern hemisphere, p < 0.0001. Seasonal influenza epidemic was coupled to El Niño, while low occurrence was coupled to La Niña. The moderate La Niña of 2010–2011 was followed by weak seasonal influenza epidemic. The influenza pandemic of 2009–2010 followed the moderate El Niño of 2009–2010, which had three peaks. Spectrograms showed time-varying periodicities of 6–48 months for ENSO, 6–24 months for influenza in the northern hemisphere, and 6–12 months for influenza in the southern hemisphere. Cross spectrograms showed time-varying periodicities at 6–36 months for ENSO and influenza in both hemispheres, p < 0.0001. Phase plots showed that influenza time series lagged ENSO in both hemispheres. Severity of seasonal influenza increases during El Niño, but decreases during La Niña. Coupling of seasonality, timing, and severity of influenza epidemics to the strength and waveform of ENSO indicate that forecast models of El Niño should be integrated into surveillance programs for influenza epidemics.

ICAM-1 regulates the survival of influenza virus in lung epithelial cells during the early stages of infection

Intercellular cell adhesion molecule-1 (ICAM-1) is an inducible cell surface glycoprotein that is expressed on many cell types. Influenza virus infection enhanced ICAM-1 expression and messenger RNA levels. Human bronchial epithelial cells (HBEpC) and nasal epithelial cells, on exposure to different strains of influenza virus (H1N1, H3N2, and H9N1) showed significant increase in ICAM-1 gene expression (p<0.001) along with the ICAM-1 protein levels (surface and secreted). Depleting ICAM-1 in HBEpC with ICAM-1 siRNA and subsequently infecting with H1N1 showed increased viral copy numbers. Influenza virus infection in HBEpC resulted in up-regulation of NF-ĸB protein and the lack of ICAM-1 decreased NF-ĸB activity in NF-ĸB luciferase reporter assay. Addition of exogenous IL-1β to HBEpC induced the ICAM-1 expression and decreased matrix gene copy number. Taken together, HBEpC induced ICAM-1 plays a key role in modulating the influenza virus survival possibly through the NF-ĸB pathway.

Influenza virus survival in aerosols and estimates of viable virus loss resulting from aerosolization and air-sampling

Using a Collison nebulizer, aerosols of influenza (A/Udorn/307/72 H3N2) were generated within a controlled experimental chamber, from known starting virus concentrations. Air samples collected after variable suspension times were tested quantitatively using both plaque and polymerase chain reaction assays, to compare the proportion of viable virus against the amount of detectable viral RNA. These experiments showed that whereas influenza RNA copies were well preserved, the number of viable viruses decreased by a factor of 10(4)-10(5). This suggests that air-sampling studies for assessing infection control risks that detect only influenza RNA may greatly overestimate the amount of viable virus available to cause infection.

Virgin Coconut Oil Supplementation Increased the Survival of Avian Influenza Virus (H5N1) Infected Chicken

Virgin Coconut Oil Supplementation Increased the Survival of Avian Influenza Virus (H5N1) Infected Chicken

Humidity and respiratory virus transmission in tropical and temperate settings.

Influenza and respiratory syncytial virus (RSV) are similarly structured viruses with similar environmental survival, but different routes of transmission. While RSV is transmitted predominantly by direct and indirect contact, influenza is also transmitted by aerosol. The cold, dry conditions of temperate winters appear to encourage the transmission of both viruses, by increasing influenza virus survival in aerosols, and increasing influenza and RSV survival on surfaces. In contrast, the hot, wet conditions of tropical rainy seasons appear to discourage aerosol transmission of influenza, by reducing the amount of influenza virus that is aerosolized, and probably also by reducing influenza survival in aerosol. The wet conditions of tropical rainy seasons may, however, encourage contact transmission of both viruses, by increasing the amount of virus that is deposited on surfaces, and by increasing virus survival in droplets on surfaces. This evidence suggests that the increased incidence of influenza and RSV in tropical rainy seasons may be due to increased contact transmission. This hypothesis is consistent with the observation that tropical rainy seasons appear to encourage the transmission of RSV more than influenza. More research is required to examine the environmental survival of respiratory viruses in the high humidity and temperature of the tropics.

Survival of influenza virus on human fingers

Indirect transmission of the influenza virus via finger contamination with respiratory mucus droplets has been hypothesized to contribute to transmission in the community. Under laboratory conditions, influenza-infected respiratory droplets were reconstituted as close as possible to natural conditions. We investigated experimentally the survival of influenza A (H3N2) and A (H1N1)pdm09 viruses on human fingers. Infectious virus was easily recoverable on all fingers 1 min after fingertip contamination but then decreased very rapidly. After 30 min, infectious virus was detectable in only a small minority of subjects. Infectious viruses were detected for a longer period of time when droplets of larger size containing a higher number of particles were tested or when the viral concentration increased. A rapid decrease in infectiousness was observed when droplet integrity was disrupted. Our findings could help to set up the promotion of hand hygiene to prevent influenza hand contamination.

Red Ginseng-containing diet helps to protect mice and ferrets from the lethal infection by highly pathogenic H5N1 influenza virus

The highly pathogenic (HP) H5N1 influenza virus is endemic in many countries and has a great potential for a pandemic in humans. The immune-enhancing prowess of ginseng has been known for millennia. We aimed to study whether mice and ferrets fed with Red Ginseng could be better protected from the lethal infections of HP H5N1 influenza virus than the infected unfed mice and ferrets. We fed mice and ferrets with Red Ginseng prior to when they were infected with HP H5N1 influenza virus. The mice and ferrets fed with a 60-day diet containing Red Ginseng could be protected from lethal infections by HP H5N1 influenza virus (survival rate of up to 45% and 40%, respectively). Interferon-α and -γ antiviral cytokines were significantly induced in the lungs of mice fed Red Ginseng, compared to mice fed an unsupplemented diet. These data suggest that the diet with the immune-enhancing Red Ginseng could help humans to overcome the infections by HP H5N1 influenza virus.