Can 10× cheaper, lower-efficiency particulate air filters and box fans complement High-Efficiency Particulate Air (HEPA) purifiers to help control the COVID-19 pandemic?

Public health departments such as CDC and California Department of Public Health (CA-DPH) advise HEPA-purifiers to limit transmission of SARS-CoV-2 indoor spaces. CA-DPH recommends air exchanges per hour (ACH) of 4-6 air for rooms with marginal ventilation and 6-12 in classrooms often necessitating multiple HEPA-purifiers per room, unaffordable in under-resourced community settings. Pressure to seek cheap, rapid air filtration resulted in proliferation of lower-cost, Do-It-Yourself (DIY) air purifiers whose performance is not well characterized compared to HEPA-purifiers. Primary metrics are clean air delivery rate (CADR), noise generated (dBA), and affordability ($$). CADR measurement often requires hard-to-replicate laboratory experiments with generated aerosols. We use simplified, low-cost measurement tools of ambient aerosols enabling scalable evaluation of aerosol filtration efficiencies (0.3 to 10 µm), estimated CADR, and noise generation to compare 3 HEPA-purifiers and 9 DIY purifier designs. DIY purifiers consist of one or two box fans coupled to single MERV 13-16 filters (1″-5″ thick) or quad filters in a cube. Accounting for reduced filtration efficiency of MERV 13-16 filters (versus HEPA) at the most penetrating particle size of 0.3 µm, estimated CADR of DIY purifiers using 2″ (67%), 4″ (66%), and 5″ (85%) filters at lowest fan speed was 293 cfm ($35), 322 cfm ($58), and 405 cfm ($120) comparable to best-in-class, low-noise generating HEPA-purifier running at maximum speed with at 282 cfm ($549). Quad filter designs, popularly known Corsi-Rosenthal boxes, achieved gains in estimated CADR below 80% over single filter designs, less than the 100% gain by adding a second DIY purifier. Replacing one of the four filters with a second fan resulted in gains of 125%-150% in estimated CADR. Tested DIY alternatives using lower-efficiency, single filters compare favorably to tested HEPA-purifiers in estimated CADR, noise generated at five to ten times lower cost, enabling cheap, rapid aerosol removal indoors.

Designing Out the Risk of Infections via Aerosols by Updating Restrictions on Indoor Environments Depending on Local Incidence Rates and the Dominant SARS-Co V -2 Strain

The paper contributes to existing research on transmission of infectious diseases in indoor environments, with a focus on the SARS-Co V -2 virus, considered in an environment with a potentially high infectious risk, i.e. a university building. A multi-functional zone with variable occupancy schedules involving both students and staff is used as a case study. A computational fluid dynamics (CFD) model is developed to simulate and analyze three scenarios involving mixed, mechanical, and natural ventilation. Based on the physical and operational configuration of the selected zone, initial results show that mechanical ventilation involves areas of stagnant air (i.e. air velocity is less than 0.1m/s), while reliance on natural ventilation leads to increase in C02 levels. Hence, a mixed mode (natural and mechanical) ventilation is suggested. Then, based on the probability of the presence of (an) infected individual(s), considering the local COVID-19 incidence rate, initial estimates suggest that the Delta variant requires the air change rate (ACH) to be increased more than 1000 times, when compared to the original strain. The paper thus establishes a correlation between the prevalence of a given SARS-Co V -2 variant with the required air change rate, emphasizing the need to factor in not only the presence of infected individual(s), based on the local incidence rate, but also the viral charge of the dominant SARS-Co V -2 variant. The paper argues the need for a better controlled and optimized ventilation to ensure safer indoor environments. © 2022 IEEE.

COVID-19 Vaccination and Late-Onset Myasthenia Gravis: A New Case Report and Review of the Literature.

Myasthenia gravis (MG) is a rare autoimmune disease that is potentially threatening for patient life. Auto-antibodies targeting structures of the neuromuscular junction, particularly the acetylcholine receptor (AchR), are often found in the serum of MG patients. New-onset MG after SARS-CoV-2 vaccination has rarely been reported since the introduction of vaccination. Infections and COVID-19 infection have also been reported as possible triggers for a myasthenic crisis. We report a case of new-onset MG after receiving the mRNA COVID-19 vaccination. The patient was a 73-year-old male initially presenting with ocular symptoms and a rapid generalization. We also performed a literature revision of 26 described cases of MG after SARS-CoV-2 immunization. The patients were a majority of males with generalized late-onset MG occurring after the first dose of vaccine, similar to our patient. Only our patient showed a thymoma. Thymic mass and the positivity of AchR antibodies suggest that vaccination might have triggered a subclinical pre-existing MG with symptoms flaring. Clinicians should be aware of possible new-onset MG after COVID-19 vaccination, particularly in at-risk patients. Even though COVID-19 vaccination should be recommended in MG patients, particularly in well-compensated patients. However, more studies need to be performed in the future.

Development of a non-contact mobile screening center for infectious diseases: Effects of ventilation improvement on aerosol transmission prevention.

Under the global landscape of the prolonged COVID-19 pandemic, the number of individuals who need to be tested for COVID-19 through screening centers is increasing. However, the risk of viral infection during the screening process remains significant. To limit cross-infection in screening centers, a non-contact mobile screening center (NCMSC) that uses negative pressure booths to improve ventilation and enable safe, fast, and convenient COVID-19 testing is developed. This study investigates aerosol transmission and ventilation control for eliminating cross-infection and for rapid virus removal from the indoor space using numerical analysis and experimental measurements. Computational fluid dynamics (CFD) simulations were used to evaluate the ventilation rate, pressure differential between spaces, and virus particle removal efficiency in NCMSC. We also characterized the airflow dynamics of NCMSC that is currently being piloted using particle image velocimetry (PIV). Moreover, design optimization was performed based on the air change rates and the ratio of supply air (SA) to exhaust air (EA). Three ventilation strategies for preventing viral transmission were tested. Based on the results of this study, standards for the installation and operation of a screening center for infectious diseases are proposed.

Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.

BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

The Role of Oral Health in the Acquisition and Severity of SARS-CoV-2: A Retrospective Chart Review.

Objective: Studies have shown that gingival crevices may be a significant route for SARS-CoV-2 entry. However, the role of oral health in the acquisition and severity of COVID-19 is not known. Design: A retrospective analysis was performed using electronic health record data from a large urban academic medical center between 12/1/2019 and 8/24/2020. A total of 387 COVID-19 positive cases were identified and matched 1:1 by age, sex, and race to 387 controls without COVID-19 diagnoses. Demographics, number of missing teeth and alveolar crestal height were determined from radiographs and medical/dental charts. In a subgroup of 107 cases and controls, we also examined the rate of change in alveolar crestal height. A conditional logistic regression model was utilized to assess association between alveolar crestal height and missing teeth with COVID-19 status and with hospitalization status among COVID-19 cases. Results: Increased alveolar bone loss, OR = 4.302 (2.510 - 7.376), fewer missing teeth, OR = 0.897 (0.835-0.965) and lack of smoking history distinguished COVID-19 cases from controls. After adjusting for time between examinations, cases with COVID-19 had greater alveolar bone loss compared to controls (0.641 ± 0.613 mm vs 0.260 ± 0.631 mm, p < 0.01.) Among cases with COVID-19, increased number of missing teeth OR = 2.1871 (1.146- 4.174) was significantly associated with hospitalization. Conclusions: Alveolar bone loss and missing teeth are positively associated with the acquisition and severity of COVID-19 disease, respectively.

Role of pathogen-laden expiratory droplet dispersion and natural ventilation explaining a COVID-19 outbreak in a coach bus.

The influencing mechanism of droplet transmissions inside crowded and poorly ventilated buses on infection risks of respiratory diseases is still unclear. Based on experiments of one-infecting-seven COVID-19 outbreak with an index patient at bus rear, we conducted CFD simulations to investigate integrated effects of initial droplet diameters(tracer gas, 5 µm, 50 µm and 100 µm), natural air change rates per hour(ACH = 0.62, 2.27 and 5.66 h-1 related to bus speeds) and relative humidity(RH = 35% and 95%) on pathogen-laden droplet dispersion and infection risks. Outdoor pressure difference around bus surfaces introduces natural ventilation airflow entering from bus-rear skylight and leaving from the front one. When ACH = 0.62 h-1(idling state), the 30-min-exposure infection risk(TIR) of tracer gas is 15.3%(bus rear) - 11.1%(bus front), and decreases to 3.1%(bus rear)-1.3%(bus front) under ACH = 5.66 h-1(high bus speed).The TIR of large droplets(i.e., 100 µm/50 µm) is almost independent of ACH, with a peak value(∼3.1%) near the index patient, because over 99.5%/97.0% of droplets deposit locally due to gravity. Moreover, 5 µm droplets can disperse further with the increasing ventilation. However, TIR for 5 µm droplets at ACH = 5.66 h-1 stays relatively small for rear passengers(maximum 0.4%), and is even smaller in the bus middle and front(<0.1%). This study verifies that differing from general rooms, most 5 µm droplets deposit on the route through the long-and-narrow bus space with large-area surfaces(L∼11.4 m). Therefore, tracer gas can only simulate fine droplet with little deposition but cannot replace 5-100 µm droplet dispersion in coach buses.

Applicability evaluation of a demand-controlled ventilation system in livestock.

The distribution of agricultural and livestock products has been limited owing to the recent rapid population growth and the COVID-19 pandemic; this has led to an increase in the demand for food security. The livestock industry is interested in increasing the growth performance of livestock that has resulted in the need for a mechanical ventilation system that can create a comfortable indoor environment. In this study, the applicability of demand-controlled ventilation (DCV) to energy-efficient mechanical ventilation control in a pigsty was analyzed. To this end, an indoor temperature and CO2 concentration prediction model was developed, and the indoor environment and energy consumption behavior based on the application of DCV control were analyzed. As a result, when DCV control was applied, the energy consumption was smaller than that of the existing control method; however, when it was controlled in an hourly time step, the increase in indoor temperature was large, and several sections exceeded the maximum temperature. In addition, when it was controlled in 15-min time steps, the increase in indoor temperature and energy consumption decreased; however, it was not energy efficient on days with high-outdoor temperature and pig heat.

Mathematical modeling of ventilation in classrooms as decrease in the risk of contagion by COVID-19

In indoor spaces, there is evidence of the importance of transmission of the SARS-CoV-2 virus by air through aerosols, especially in poorly ventilated conditions. Viruses are exhaled by infected people into respiratory particles with sizes less than 50 microns (microdroplets) that are suspended in the air (aerosols) and can be transported to distances greater than 2 meters within a closed room, such as classrooms. Therefore, in closed school environments, the conditions of occupation and ventilation are essential to determine and minimize the risk of transmission of the virus. There are various techniques to physically assess the air change rate (ACH) in an indoor space or to estimate it indirectly by measuring carbon dioxide (CO2). However, these procedures could be complex for an untrained community or in the absence of a CO2 monitor. The application of mathematical models allows alternatively to evaluate the ventilation conditions from the estimation of ACH or the concentration of CO2 in an intramural space. Some mathematical models were included as part of a guide developed for the evaluation and monitoring of ventilation in school settings. In this work, the application of mass balance models is presented, under conditions of complete mixing, in a classroom in order to estimate ACH from the volume and occupation of the room. Likewise, mathematical expressions are developed to estimate the concentration of CO2 and evaluate the risk of contagion to COVID-19 in situations with and without ventilation. From simple mathematical expressions, it is contributed to the evaluation of the ventilation conditions of classrooms to avoid possible outbreaks of contagion in face-to-face education. © 2021 IEEE.

A review of solar chimney for natural ventilation of residential and non-residential buildings

The requirement for passive cooling strategies in buildings has great attention in almost all countries, where hot temperatures are predominant throughout the year. The ventilation process is a crucial necessity for a healthy lifestyle and its significance is additionally highlighted through the contemporary universal outbreak of Covid-19. One of the promising applications for cooling residential buildings is the solar chimney (SC) that is particularly convenient for hot and humid climates. The solar chimney is a natural draught passive method that utilizes available solar energy to build up the stack pressure. The solar chimney participates in elevating the cooling and heating efficiency of residential/non-residential spaces. The present article introduces an overview of the operation and performance of the SC. Studying the potential design and operating parameters influencing the SC performance for natural ventilation (NV) compared to the electrical high-energy technologies to sustain the acceptable indoor climatic conditions is important. As well, the natural ventilation for harsh climate conditions using SC only is not applicable so the enhanced solar ventilation systems are studied. Combined enhanced cooling/heating energy systems based on the solar chimney are considered as an effective strategy towards low-energy consuming buildings.

Evaluation of ventilation, indoor air quality, and probability of viral infection in an outdoor dining enclosure.

In 2020, many cities closed indoor dining to curb rising COVID-19 cases. While restaurants in warmer climates were able to serve outdoors year-round, restaurants in colder climates adopted various solutions to continually operate throughout the colder months, such as the use of single-party outdoor dining enclosures to allow for the continuation of outdoor dining. This study evaluates indoor air quality and the air exchange rate using carbon dioxide as a tracer gas in a dining enclosure (12.03 m3) and models the probability of COVID-19 infection within such an enclosure. The air exchange rates were determined during two trials for the following scenarios: (1) door closed, (2) door opened, and (3) door opened intermittently every 15 min for 1 min per opening. The probability of COVID-19 infection was evaluated for each of these scenarios for 1 hr, with occupancy levels of two, four, and six patrons. The Wells-Riley equation was used to predict the probability of infection inside the dining enclosure. The air exchange rates were lowest in the closed-door scenarios (0.29-0.59 ACH), higher in the intermittent scenarios (2.36-2.49 ACH), and highest in the open-door scenarios (3.61 to 33.35 ACH). As the number of subjects inside the enclosure increased, the carbon dioxide accumulation increased in the closed-door and intermittent scenarios. There was no identifiable accumulation of carbon dioxide in the open-door scenario. The probability of infection (assuming one infected person without a mask) was inversely proportional to the airflow rate, and ranged from 0.0002-0.84 in the open-door scenario, 0.0034-0.94 for the intermittent scenarios, and 0.015-1.0 for the closed-door scenarios. The results from this study indicate that under typical use, the indoor air quality inside dining enclosures degrades during occupancy. The probability of patrons and workers inside dining enclosures being infected with COVID-19 is high when dining or serving a party with an infected person.

Erythrocytes Induce Vascular Dysfunction in COVID-19.

Current knowledge regarding mechanisms underlying cardiovascular complications in patients with COVID-19 is limited and urgently needed. We shed light on a previously unrecognized mechanism and unravel a key role of red blood cells, driving vascular dysfunction in patients with COVID-19 infection. We establish the presence of profound and persistent endothelial dysfunction in vivo in patients with COVID-19. Mechanistically, we show that targeting reactive oxygen species or arginase 1 improves vascular dysfunction mediated by red blood cells. These translational observations hold promise that restoring the redox balance in red blood cells might alleviate the clinical complications of COVID-19-associated vascular dysfunction.

Indoors ventilation in times of confinement by SARS-CoV-2 epidemic: A comparative approach between Spain and Italy.

With the arrival of the SARS-CoV-2 coronavirus, the scientific academia, as well as policymakers, are striving to conceive solutions as an attempt to contain the spreading of contagion. Among the adopted measures, severe lockdown restrictions were issued to avoid the diffusion of the virus in an uncontrolled way through public spaces. It can be deduced from recent literature that the primary route of transmission is via aerosols, produced mainly in poorly ventilated interior areas where infected people spend a lot of time with other people. Concerning contagion rates, accumulated incidence or number of hospitalizations due to COVID-19, Spain, and Italy have reached very high levels. In this framework, a regression analysis to assess the feasibility of the indoor ventilation measures established in Spain and Italy, with respect to the European framework, is here presented. To this aim, ten cases of housing typology were and analyzed. The results show that the measures established in the applicable regulations to prevent and control the risk of contagion by aerosols are not adequate to guarantee a healthy environment indoors. The current Italian guidelines are more restrictive than in Spain, yet the ventilation levels are still insufficient in times of pandemic.

Natural ventilation strategy and related issues to prevent coronavirus disease 2019 (COVID-19) airborne transmission in a school building.

The World Health Organization (WHO) announced that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may spread through aerosols, so-called airborne transmission, especially in a poorly ventilated indoor environment. Ventilation protects the occupants against airborne transmission. Various studies have been performed on the importance of sufficient ventilation for diluting the concentration of virus and lowering any subsequent dose inhaled by the occupants. However, the ventilation situation can be problematic in public buildings and other shared spaces, such as shops, offices, schools, and restaurants. If ventilation is provided by opening windows, the outdoor airflow rate depends strongly on the specific local conditions (opening sizes, relative positions, climatic and weather conditions). This study uses field measurements to analyze the natural ventilation performance in a school building according to the window opening rates, positions, and weather conditions. The ventilation rates were calculated by the tracer gas decay method, and the infection risk was assessed using the Wells-Riley equation. Under cross-ventilation conditions, the average ventilation rates were measured at 6.51 h-1 for 15% window opening, and 11.20 h-1 for 30% window opening. For single-sided ventilation, the ventilation rates were reduced to about 30% of the values from the cross-ventilation cases. The infection probability is less than 1% in all cases when a mask is worn and more than 15% of the windows are open with cross-ventilation. With single-sided ventilation, if the exposure time is less than 1 h, the infection probability can be kept less than 1% with a mask. However, the infection probability exceeds 1% in all cases where exposure time is greater than 2 h, regardless of whether or not a mask is worn. Also, when the air conditioner was operated with a window opening ratio of 15%, power consumption increased by 10.2%.

Investigation of potential aerosol transmission and infectivity of SARS-CoV-2 through central ventilation systems.

The COVID-19 pandemic has raised concern of viral spread within buildings. Although near-field transmission and infectious spread within individual rooms are well studied, the impact of aerosolized spread of SARS-CoV-2 via air handling systems within multiroom buildings remains unexplored. This study evaluates the concentrations and probabilities of infection for both building interior and exterior exposure sources using a well-mixed model in a multiroom building served by a central air handling system (without packaged terminal air conditioning). In particular, we compare the influence of filtration, air change rates, and the fraction of outdoor air. When the air supplied to the rooms comprises both outdoor air and recirculated air, we find filtration lowers the concentration and probability of infection the most in connected rooms. We find that increasing the air change rate removes virus from the source room faster but also increases the rate of exposure in connected rooms. Therefore, slower air change rates reduce infectivity in connected rooms at shorter durations. We further find that increasing the fraction of virus-free outdoor air is helpful, unless outdoor air is infective in which case pathogen exposure inside persists for hours after a short-term release. Increasing the outdoor air to 33% or the filter to MERV-13 decreases the infectivity in the connected rooms by 19% or 93% respectively, relative to a MERV-8 filter with 9% outdoor air based on 100 quanta/h of 5 µm droplets, a breathing rate of 0.48 m3/h, and the building dimensions and air handling system considered.

Nicotinic cholinergic system and COVID-19: In silico evaluation of nicotinic acetylcholine receptor agonists as potential therapeutic interventions.

SARS-CoV-2 infection was announced as a pandemic in March 2020. Since then, several scientists have focused on the low prevalence of smokers among hospitalized COVID-19 patients. These findings led to our hypothesis that the Nicotinic Cholinergic System (NCS) plays a crucial role in the manifestation of COVID-19 and its severe symptoms. Molecular modeling revealed that the SARS-CoV-2 Spike glycoprotein might bind to nicotinic acetylcholine receptors (nAChRs) through a cryptic epitope homologous to snake toxins, substrates well documented and known for their affinity to the nAChRs. This binding model could provide logical explanations for the acute inflammatory disorder in patients with COVID-19, which may be linked to severe dysregulation of NCS. In this study, we present a series of complexes with cholinergic agonists that can potentially prevent SARS-CoV-2 Spike glycoprotein from binding to nAChRs, avoiding dysregulation of the NCS and moderating the symptoms and clinical manifestations of COVID-19. If our hypothesis is verified by in vitro and in vivo studies, repurposing agents currently approved for smoking cessation and neurological conditions could provide the scientific community with a therapeutic option in severe COVID-19.

NORA: Considerations during COVID 19 Pandemic-The New York Experience.

Hospitals rapidly developed new procedure and protocols and engaged in emergency construction projects to adapt their facilities and procedures to provide safe and effective patient care during the COVID- 19 pandemic surge in the New York metropolitan area. Physical and procedural revisions were necessary in the operating room to continue to care for emergent patients both with and without COVID. Similar adaptions in non operating room procedure suites, recognized commonly as Non-operating Room Anesthesiology (NORA), necessitated the engagement of multiple departments in order to develop protocols and to redesign procedural areas. This article describes in detail the collaborative planning, construction and preparation implemented in two academic medical centers with regard to their various NORA programs. In developing patient care, personal protective equipment training and repurposing of procedure suites, the multidisciplinary collaborative teams have taken into consideration the professional national societies governing Gastroenterology, Cardiology, and Interventional Radiology.

A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. METHODS: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. DISCUSSION: This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04343963 (registered on April 14, 2020).

How nicotine can inhibit cytokine storm in the lungs and prevent or lessen the severity of COVID-19 infection?

Statistical surveys of COVID-19 patients indicate, against all common logic, that people who smoke are less prone to the infection and/or exhibit less severe respiratory symptoms than non-smokers. This suggests that nicotine may have some preventive or modulatory effect on the inflammatory response in the lungs. Because it is known that the response to, and resolution of the SARS-CoV-2 infection depends mainly on the lung macrophages, we discuss the recent scientific findings, which may explain why and how nicotine may modulate lung macrophage response during COVID-19 infection.