On March 11, 2020, the World Health Organization declared the spread of the novel coronavirus (COVID-19) a global pandemic [1]. As a primary measure to control the spread of the virus, many governments worldwide recommended staying at home and practicing social distancing, dramatically affecting people’s daily lives [2-4]. Health care represents one of the sectors most affected by the adverse effects of the COVID-19 pandemic [5]. Prolonged rules of social distancing and stay-at-home directions caused relevant difficulties in carrying out several in-hospital clinical activities [6,7], and the sudden interruption of medical education and training programs [8-10].

In such times of isolation and limited resources due to the COVID-19 crisis, information and communication technologies (ICTs) have empowered medical institutions to meet mental health and learning needs with scalable solutions [11,12]. Virtual reality (VR) represents an ICT development with the potential to revolutionize clinical support and education [13-17].

By definition, VR is a set of technologies, including head-mounted displays (HMDs), computers, and mobile devices, that can immerse users in a 3D environment to different degrees [18-21], from a simple presentation on a 2D display screen system (ie, desktop VR) up to highly immersive systems (ie, immersive VR) that use HMDs.

VR in the last decade has become a game changer for the health care sector in more than one way [22-25], representing a helpful instrument both for the treatment of several health conditions and for medical education and training [22,25-28]. This technology has been successfully applied to a wide range of mental disorders [29,30], including anxiety [31-33] and depression [34]. Furthermore, VR is being used in physical rehabilitation for improving motor function, fitness, movement quality, and mobility [35,36], and it has also been adopted as an enjoyable method for managing pain [37-40]. Regarding education and training, VR was greatly appreciated by medical and nursing students [41-43], and proved to play a crucial role in improving medical knowledge [44-46] and fostering surgical skills [44,46,47].

Therefore, during the COVID-19 crisis, VR has the potential to supplement the traditional in-hospital medical training and treatment [48], and may increase access to training and therapies in various health care settings [49,50].

Since, to the best of our knowledge, no previous work has investigated the use of health care–targeted applications of VR during the COVID-19 crisis, this systematic review aimed to describe the literature on this topic.

A systematic search of the literature was performed on March 3, 2022, by 2 of the authors (FP and AP) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [51]. The review was preregistered (September 29, 2021) in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY; INPLASY202190108). The search databases were PsycINFO, Web of Science, and MEDLINE.

Two authors (FP and AP) established clear inclusion criteria to determine papers’ eligibility for inclusion in the review. Only studies meeting the following criteria were considered eligible for inclusion: (1) type of participant: all human participants (clinical and nonclinical population); (2) intervention: VR; (3) comparators: usual intervention, non-VR group, or none; (4) outcomes: focused on health care–targeted applications of VR during the COVID-19 pandemic; and (5) study design: randomized controlled trial (RCT), quantitative nonrandomized study (eg, nonrandomized controlled trial and case-control study), quantitative descriptive study (eg, survey, case series, and case report), or mixed methods study.

Papers published in English between December 2019 and March 2022 in peer-reviewed journals were selected and subjected to the inclusion criteria outlined above.

Studies were excluded if they (1) did not use VR; (2) did not focus on the applications of VR for the treatment of health conditions, or for medical education and training during the COVID-19 pandemic; (3) did not describe research conducted after the outbreak of the COVID-19 crisis; (4) did not specify the period when the study was conducted; (5) did not include outcome measures or did not include complete results; (6) did use only qualitative data; and (7) were letter to the editor articles, commentaries, or reviews.

The search string was as follows: “[(virtual reality)] AND [(COVID-19) OR (coronavirus) OR (SARS-CoV-2) OR (healthcare)].”

Initially, 2 authors (FP and AP) checked the titles and abstracts of identified articles to determine their eligibility. Subsequently, they independently reviewed the full text of potentially eligible papers. A consensus between the authors (FP and AP) resolved disagreements. When papers provided insufficient data for inclusion in the analysis, the corresponding authors were contacted to provide additional data. Five additional articles emerged via hand-searching and reviewing the reference lists of relevant papers.

We used the Mixed Methods Appraisal Tool (MMAT) [52] to assess the methodological quality of the studies included and the risk of bias. Studies could be awarded a score of 0, 25, 50, 75, or 100 (with 100 being the highest quality). The MMAT has high reliability and efficiency as a quality assessment protocol and can concomitantly appraise methodological quality across various empirical research [53]. Two authors (FP and AP) independently assessed the studies’ quality. Interrater reliability was calculated with Cohen kappa [54], using the software package SPSS (IBM Corp).

Two authors (FP and AP) independently extracted the following data.

The search strategy retrieved 2503 records published after December 2019. A total of 1687 studies remained after deduplication and language examination, and 905 records were excluded after the first screening, and title and abstract analysis. Full-text copies of the 782 remaining studies were obtained and subjected to further evaluation. After reading the full-text copies, 743 studies were excluded based on our exclusion criteria, resulting in 39 studies being included in our systematic review (Figure 1).

Interrater reliability was 0.827, representing substantial agreement [67]. Within this systematic review, the distribution of MMAT scores varied significantly with the study design (Table 2). Nineteen studies (49%) met the MMAT quality assessment score of 75% or above, implying that much of the research in this area is of high quality (Multimedia Appendix 1). Nevertheless, the quality scores varied substantially according to the study design.

Of the 39 studies included, 31 tested the efficacy of specific VR systems (Table 4), while 8 investigated the general use of VR in different samples (eg, mental health professionals and doctors) (Multimedia Appendix 3) [86-89,94,97,98,103].

This systematic review examined studies conducted on VR applications in medicine during the COVID-19 pandemic, with a focus on using VR to treat health conditions and in medical education and training. After applying the inclusion criteria, 39 papers were included and analyzed.

From this systematic review, VR was found to be useful during the COVID-19 pandemic for reducing stress (eg, [75,80,96]), anxiety [91], depression [95], and pain [70], and promoting physical activity [79,90]. This technology has been successfully used in healthy people (eg, [74,86,92,94]); COVID-19 ICU health care workers [80,81]; patients with various diseases, including mild cognitive impairment [91], mild depressive disorders [95], and cerebral palsy [79]; chief complaints of fear of COVID-19 [85]; and individuals treated in the ICU due to COVID-19 [49,71,96].

VR has been successfully applied for decades to diminish stress, anxiety, depression, and pain [38,40,106-110]. Besides, this technology, especially immersive video games [111,112], stimulates physical activity [108], with long-term positive outcomes on mental and physical health [113,114]. What is new from the past, as noted in this review, is that VR is no longer used only in the specialist’s office or at the hospital but is also used remotely. The release of current standalone and low-cost mobile VR systems, thanks to the high ease of use and limited costs, has made this technology feasible for everyday in-home use [115]. Studies from this review showed that VR during the COVID-19 pandemic has begun to be adopted into mainstream clinical practice for remote psychological support [97,98]. This fact appears relevant since VR home-based training represents new promising interventions for remote support [98,116,117].

From this review, not only VR environments developed ad hoc, but also commercial contents (eg, VR video games downloaded from the Steam platform, and 360° videos and photos available on YouTube) were useful for diminishing stress [92], anxiety [91], and depression [95], and for promoting physical activity [90]. These findings seem interesting since using commercial off-the-shelf VR video games and experiences for promoting mental health and physical activity could have several advantages, including their low cost and ready-to-use format, their advanced graphic quality, and the possibility to reach millions of individuals worldwide [107,118].

The second main result of this systematic review is that during the COVID-19 pandemic, VR was a helpful learning tool for medical education and training in several areas, including emergency medicine, nursing, pediatrics, radiology, and cardiology (eg, [100-102]). This technology has been successfully used for teaching various topics, including neuroanatomy and clinical anatomy (eg, [84,93]). VR has also been adopted to train COVID-19–related skills among doctors and nurses [68,73]. Studies that emerged from this systematic review showed that, where available, high-fidelity immersive VR was adopted heavily after the outbreak of the COVID-19 pandemic [88,103].

Several previous studies proved the usefulness of VR for the training of medical students and nurses [43] and for teaching many medical topics and procedures, such as clinical anatomy [41,45] and radiation oncology [42]. This technology is considered a superior educational modality in comparison to passive teaching methods, such as learning from a textbook, slideshow, or lecture, thanks especially to the greater involvement of individuals in the learning process [119-121].

This review, with regard to treatment, showed that during the COVID-19 pandemic, VR started to be used for medical education and training in face-to-face sessions and remotely. This flexibility of access allowed the adoption of this technology into medical education curricula for both in-person and home-based activities [122]. Medical students mostly agreed that online teaching using VR compensated for the suspension of face-to-face medical education and reported this technology as the best alternative to physical learning [89].

Some studies that emerged in this review used content in multiuser VR, including social VR platforms [82]. Such VR environments are an emerging diverse group of multiuser online applications creating new opportunities for remote simulation and communication, and facilitating and extending the existing communication channels of the physical world [123,124]. Although its exploration has been limited so far, education using social VR will be increasingly relevant in the next few years. Indeed, major technology companies are making huge investments in the so-called “metaverse” (ie, a simulated digital environment that incorporates VR and other technologies, including augmented reality and artificial intelligence, to build spaces where users can interact as in the actual world) [125]. “Metaversities” could become the universities of the future [126].

In this systematic review, VR was also an effective educational tool for increasing public understanding and knowledge of the COVID-19 pandemic [76] and COVID-19 vaccination intentions [69]. This result, in line with previous literature [127,128], stresses the potential of VR as a useful and innovative tool for promoting scientific and medical knowledge among the general population. VR can improve health awareness and assist in health-related decision-making for the general population [129], increasing the overall motivation and engagement and leading to a more effective transfer of medical knowledge and comprehension of information [130,131]. In turn, this could improve individuals’ overall health, decrease hospitalization rates, and save long-term physician consultation costs [129].

Moreover, studies from this systematic review showed the usefulness of VR for treating health problems and for medical education and training in both the high (ie, immersive VR) and low immersion (ie, desktop VR) formats. This result appears important as these VR systems have very different characteristics and costs [132-134]. On the one hand, as emerged from studies included in this review (eg, [68,70]), immersive VR offers advantages over desktop VR [62,135]. However, desktop VR has the main advantages of being more readily usable and accessible, and having a lower cost.

Various types of HMDs (ie, PC-based, mobile, and standalone) and contents (ie, 360° videos and photos, virtual environments, VR games, and embodied virtual agents) have been used with positive results in medicine during the COVID-19 crisis (eg, [48,73,101]). This underscores how nowadays it is possible to choose among different VR hardware and software. To select the potentially most effective ones, it is critical to reason about the specific goal of VR use [136]. For example, in the case of VR for relaxation, it may be sufficient to include a low-cost mobile system and 360° videos or commercial off-the-shelf VR games. The same is true when VR is adopted to offer doctors and nurses “soft skills” (eg, problem-solving, communication, and interpersonal skills) training. On the other hand, in the case where VR is used for complex operations, simulation training, a PC-based system, haptic devices, and specially created virtual content should be used. In fact, in this case, the graphical and sensory fidelity of VR are crucial [137,138].

In addition to offering data in favor of the usefulness of VR in the health care sector, this review also raises some critical reflections on the possible limits of using this technology for these aims.

First, some health care workers experienced difficulties in using VR [48]. Due to a lack of knowledge of this technology, many individuals may find it challenging to use VR. To overcome the mentioned obstacle, governments and other societal bodies (eg, medical societies, medical schools, and residency training programs) should provide information about VR (eg, through training courses dedicated to health care practitioners and mental health professionals). They should offer clear guidelines for correctly using this technology in mental health, and medical education and training [15].

Second, when the graphic quality of the virtual experience was perceived as too low, users had difficulties comprehending a target scenario [73,87]. To prevent graphical or technical problems (eg, breakdown or problems with interaction) [139,140], with potential detrimental effects on treatment and learning outcomes [137,141], the principles and practices of user-centered design are recommended [142,143]. Many VR-based treatment, and medical education and training programs are currently taking a technology approach rather than a human-centered approach, which can lead to limited impact of VR in these fields. Due to the close bond between the user and the system within virtual environments, it may be impossible to segregate human factors from design issues when striving to achieve the potential of VR [144]. For this reason, it appears critical that a psychologist with expertise in human-computer interaction always be included in the team developing virtual experiences for the medical field.

Third, a primary issue in using this technology in the mental health panorama is related to its costs. The price of HMDs range from US $300 to US $1500. In the case of VR content developed ad hoc, the costs for implementation are high. One way to overcome the economic barrier of VR could be to use standalone or low-cost mobile systems [115,145] and, whenever possible, commercially available content [107,118]. Another solution could be providing hospitals with a certain number of VR systems to be available for their patients and staff for free [15].

More studies should be undertaken to expand the limited literature on home-based VR for treatment, and medical education and training. Multiuser VR platforms could be studied more deeply in education and as tools to implement future interventions for treating mental and physical health conditions. More research should be conducted to test the efficacy of commercial off-the-shelf VR experiences for treatment and in educational settings. Limitations and possibilities of VR systems with high versus low immersion require further investigation, for example, through RCT studies comparing their effectiveness for clinical or learning outcomes. It might be worth investigating the longer-term effects of VR on such outcomes. Finally, the number of desired or needed VR sessions and the specific time to spend using VR remain matters of debate.

This review summarizes health care-targeted applications of VR during the COVID-19 pandemic based on specific keywords used in the search string, the databases included, and the review’s time period. Therefore, certain articles could have been missed. Second, only articles written in English and peer reviewed were included. Hence, preprints and gray literature were left out, which may have introduced some biases. Third, a meta-analysis was not possible due to the heterogeneity of the included studies. Fourth, the quality assessment performed using the MMAT suggests that even if much of the research in this area is of high quality, methodological concerns are significant issues for many studies.

VR has been applied frequently during the COVID-19 pandemic in medicine, with positive effects for treating several health conditions and for medical education and training. Some barriers need to be overcome for a broader adoption of VR in the health care panorama. Based on these findings, it is possible to offer certain VR-based programs even remotely for therapeutic or educational purposes, and not only VR environments developed ad hoc, but also commercial content can be helpful in clinical or educational support. Moreover, VR-based interventions have the potential to be used effectively for the treatment of several mental and physical conditions, as well as for medical education and training in both immersive and desktop systems. Various VR contents are helpful in treating health problems and for medical education and training, including 360° videos and photos, VR games, and embodied virtual agents.