## 3 Applications of Cold Atmospheric Pressure Plasma
### Medicine
Promising methods include light-based therapies (antimicrobial blue light, antimicrobial photodynamic inactivation, ultraviolet light, pulsed light) and CAPP [63]. CAPP in particular seems to be highly effective against multidrug resistant organisms (e.g., Methicillin-resistant _Staphylococcus aureus_, vancomycin-resistant enterococci), regardless of the kind of germ [42; 47; 49; 64]. Clearly, the efficiency of the elimination process is highly dependent on the plasma device, process parameters and environmental factors (e.g., wound type, extracellular matrix) [65]. CAPP did not show any bacterial adaptation after consecutive treatments [63]. [PERSON] et al. studied two clinically significant ESKAPE (an acronym for six virulent and antibiotic resistant pathogens) bacteria. After the plasma treatment, the decrease in bacterial load (_P. aeruginosa_ and methicillin-resistant _S. aureus_) was comparable to the inactivation using biocide (chlorexidine) and antibiotics (ciprofloxacin, daptomycin). The CAPP device (RF source from two parallel brass grids operating with helium) generated RONS in bacteria, disrupted membrane integrity and reduced the bacterial load. They treated the samples using the plasma afterglow, which inactivated the bacteria independently of their growth mode (planktonic or biofilm) [66]. Safety and bactericidal efficiency of CAPP against _Pseudomonas aeruginosa_ was studied by [PERSON] et al. Their DBD plasma treatment (4-6 min) had bactericidal properties, but it did not induce mutations, apoptosis and DNA damage or affected the wound healing process in in vitro and ex vivo rat wound models [65]. The in vitro study of [PERSON] et al. evaluated the bactericidal efficacy of CAPP (plasma jet using air) on a strain of super multidrug-resistant _P. aeruginosa_ (aerobic Gram-negative  
Figure 2: Schematic illustration of plasma inactivation of viruses and bacteria using CAPP treatment. backillus causing various infections, such as pneumonia, bloodstream, skin and soft tissue infections). Both direct and plasma activated liquid treatments resulted in a decrease in cell growth (based on the colony-forming unit assay). The direct CAPP exposure was more effective, inducing higher intracellular ROS levels. Furthermore, the disruption of membrane integrity was also more effective based on immunofluorescence images [67]. Gas plasma technology has been under research for more than 50 years due to its decontaminating properties and the majority of work has been focused on bacteria. However, contamination with infectious viruses also threatens human and animal health. The antiviral activity of CAPP is a younger but evolving research area. For example, [PERSON] et al. observed that CAPP has an antiviral effect against herpes simplex virus type 1 (HSV-1). The effect was measurable after reducing the viral load by 100-fold [68]. [PERSON] et al. efficiently inactivated different kinds of bacteriophages (including double-stranded DNA, single-stranded DNA and RNA bacteriophages) using CAPP treatment. Damaging of nucleic acids and proteins was achieved using argon and artificial air. Antiviral ability of plasma-activated water could also be a promising disinfection method to prevent the spread of viral diseases [56]. The paper of [PERSON] et al. provided a comprehensive overview about the achievements in the plasma-mediated inactivation of viruses. Their review discusses the inactivation of enteric viruses (e.g., norovirus, adenovirus, hepatitis A virus), respiratory viruses (influenza A and B, SARS-CoV-2), sexually transmitted viruses (e.g., HIV) and animal viruses (e.g., avian influenza virus, porcine reproductive and respiratory syndrome virus) [24]. During viral pandemics, like the COVID-19 crisis, respiratory viruses are responsible for over a million deaths [69]. In 2020, there has been an enormous research effort to use CAPP technology as an antiviral treatment [24]. [PERSON] et al.