Dependency and Vulnerability of Intensive Care Medicine in Times of COVID-19 Crisis

Background. Since December 2019, Coronavirus Disease-2019 (COVID-19) spread rapidly all over the world, resulting in pandemic. Through high hospitalization rates and via potentially exponential expansion of the disease, the COVID-19 crisis places a tremendous strain on healthcare systems, especially on limited numbers of hospital and Intensive Care Unit (ICU) – beds and equipment. Methods. The aim of this study was to elucidate the possible dependency of ICUs in European Countries with Austria as a pars pro toto in particular on long transglobal supply chains and its potential vulnerability by reported shortages of essential medicines and limited capacities in times of globalization and asserted economic advantages versus the pandemic threat of COVID-19. From 3 April to 8 April 2020 we performed a short survey with heads of Austria’s ICU-wards in different institutions following a structured questionnaire to enquire their personal experience and assessment. Results. We surveyed nearly half of the head physicians of ICUs (n=40) in Austria. 55 percent (n=22) are already treating COVID-19 affected patients at their ICU department. Only 45 percent (n=18) of them had received the amount of personal protective equipment they deemed enough, and 90 percent (n=36) of surveyed ICUs were already informed about shortage supplies concerning personal protective equipment. 45 percent (n=18) already reported infections within their medical personnel. 35 percent (n=14) already reported supply diculties in several pharmaceuticals, whereas 73 percent (n=29) were informed or already warned by their economic or purchase departments about further potential or real shortages concerning essential pharmaceuticals in near future. Conclusions. Summarizing the results of our survey we would like to draw attention to the lessons we can learn from the COVID-19 crisis in the European Union: European Countries with Austria as a pars pro toto should establish a national production of key equipment and disposables ,at least a minor part of personal protective equipment as well as key pharmaceuticals. European countries need to improve far distance supplies and invest in maintaining critical infrastructure in those with limited capacities as health ICUs in


Background
At the end of 2019, a series of epidemic pneumonia cases caused by a novel coronavirus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China (1,2). Since then the SARS-CoV-2 spread rapidly all over the world, resulting in a pandemic, which was termed On 30 January 2020 COVID-19 had been declared a "public health emergency of international concern" by the WHO and on 11 March 2020 COVID-19 had been assessed a pandemic for the rst time since the H1N1 pandemic in 2009/2010 (3). As of beginning of April 2020 there are far more than a total of 300 000 con rmed cases and more than 20 000 COVID-19 related deaths in Europe (4), Austria being one of the rst countries affected after the European outbreak in Italy. Through high hospitalization rates and via potentially exponential expansion of the disease, the COVID-19 crisis places a tremendous strain on healthcare systems, especially on limited numbers of hospital and Intensive Care Unit (ICU) -beds and thus necessitate rapid action and countermeasures.
According to the Austrian structural plan of health (Österreichischer Strukturplan Gesundheit, OESG) and the Organization for Economic Co-operation and Development (OECD) a total of 2.547 ICU-beds are registered in Austria, representing a rate of 28,9 beds per 100.000 population (5). Although the capacity of ICU-beds is higher than in other countries the COVID-19 crisis led to several concerns in Austria's health care system (6). Especially the adequate supply of su cient personal protective equipment (PPE), which is utterly needed in care of infectious COVID-19 patients. This lack of supply turned out as one of the most pressing issues during pandemic all over Europe, since Austria like many other countries of the European Union (EU) relies on supplies from Asia, which were delayed since production fell behind, and global demand skyrocketed as a result of the COVID-19 pandemic.
We therefore tried to elucidate the possible dependency of ICUs in Austria in particular on long transglobal supply chains and its potential vulnerability by reported shortages of essential medicines and limited capacities in times of globalization and asserted economic advantages versus the pandemic threat of COVID-19.

Methods
We performed a short telephone survey with heads of ICU-wards in different institutions following a structured questionnaire that has been developed especially for this study to enquire their personal experience and assessment. An additional le shows this questionnaire in detail (see Additional File 1). We started our questioning on 3 April 2020 ongoing until 8 April 2020. At that time containment measures with exit restrictions, starting on 16 March 2020, has lasted for a time span of three weeks. Due to the dynamic situation during pandemic with constantly changing export bans and travel restrictions especially in our neighboring countries the questionnaire represents a current snapshot of the situation in that time.
Heads of ICU were called twice, in case of temporary unavailability a return call was asked, or alternatively heads of institutional economic or purchase departments were interrogated.
A descriptive statistical analysis was performed using IBM SPSS 26. Continuous variables are described by median and mean.

Results
Within days we surveyed roughly half (n = 40) of the head physicians of ICUs in Austria. Thirty-six percent (n = 21) hospitals of the primary sector, 55% (n = 15) hospitals of the secondary sector and 29% hospitals (n = 4) of the tertiary sector were included in the study. Percentages based on Austria's total number of hospitals of each sector (7). Detailed results are listed in Table 1.  Table 2 and graphic illustration of results is shown in Fig. 1. According to the estimation of heads of ICUs the duration of pandemic should not last more than 6 weeks averagely without facing di culties in storage and availability of supply (Table 5).    Fig. 3). As a result, 28% of ICUs reported di culties in lling the duty roster due to suddenly implemented travel restrictions, others could compensate because almost 68% were reporting problems in boarder crossing of personnel ( Table 5). 45% of institutions already reported cases of COVID-19 illness and quarantine measures within their medical personnel two weeks after start of containment measures.

Discussion
Our data show the dependency of ICUs in Austria in particular on long transglobal supply chains of PPEs and essential pharmaceuticals and thus its non-insigni cant vulnerability by reported shortages in times of COVID-19. As seen in our results, 90 percent of ICUs registered supply disruptions of PPE and 35% registered shortages of far more than 3 different pharmaceuticals. 78 percent of questioned ICUs feared or were already informed about further supply di culties concerning PPE in near future. These results were also re ected in assessments of the heads of surveyed ICUs. A maximum duration of pandemic of 6 weeks without serious impact on health care system was estimated by most chief physicians mainly depending on availability of PPE and pharmaceuticals. Not only dependency on these factors was notably but also on commuting medical personnel from neighboring countries that made up on average 12% of medical personnel generally. Therefore, these three factors can be identi ed as the most pressing issues in times of pandemic.
Although Austria seems to be in a comparably favorable condition in times of COVID-19 crisis, this is mainly the result of preparation of high capacities (on average nearly 75%) that ICUs can provide especially for COVID-19 patients and lucky coincidences. As the rst affected country inside the EU, Italy is one of the most affected countries in the EU. At that time, this virus was new, and not much was known about it, leading to plausible misjudgments and therefore Italy's health care system got overwhelmed by suddenly high volumes of COVID-19 patients and limited hospital capacity during u-season. Like in many other countries, hospitals tend to run close to full capacity, with up to 87% average occupancy (10).
From Italy's experience Austria could draw attention to lessons learned from COVID-19 pandemic and has relatively early taken strict measures to avoid transmission, such as social distancing, school closures and event cancellations. With the aid of these restrictions time was gained to prepare hospitals as good as possible, expand testing capacity and thus keep death rates low. Additionally, the fact that people coming from regions of high population density such as Vienna or Lower Austria had holiday season a few weeks before outbreak of COVID-19 in Tyrol and thus could not visit these areas with high proportion of infected people resulting in moderately high infection rates in urban areas. Also, due to relatively early announced travel warnings majority of the Austrian population did not attend, for example, the carnival in Venice, which could have resulted in massive viral transmission.
Nonetheless in contrast to the positive ndings of our survey we could elaborate on three major issues of Austria's ICU in ghting COVID-19: First, in our survey more than a half of responding heads of ICUs in Austria stated not getting enough high-class disposable PPE allocated for their employees and nearly all of them reported supply di culties. About a maximal duration of pandemic of up to 6 weeks without serious negative impacts on our health system was speculated by responding heads of ICU (chief physicians), mainly arguing by stable supply chains of PPE.
In this context, we may underline that for adequate protection of medical personnel especially during the performance of aerosol generating procedures such as intubation bronchoscopy and suctioning a PPE is indispensable (9). Shortages result in inability of health care workers to protect themselves or their patients from being infected and thus will infect others (11). In most affected countries such as Italy as on 30 March 2020 9% of medical personnel got infected (10, 12), many of whom thereafter died. Since the outbreak of COVID-19 pandemic the demand on PPE increased exponentially, soon leading to depleted supplies. According to the WHO the industry must increase manufacturing by 40 per cent to meet rising global demand (11). Due to economic globalization of health care and decentralized production of disposables such as PPE to save costs, like many other countries in the EU, Austria buys masks, goggles, impervious gown and gloves mainly from Asia, resulting in high dependency of secure global supply chains. Closing of borders worldwide and ban of exports of Asia therefore aggravated the shortage of PPE. But also, within Europe, the crisis has piled stress onto intra-European supply chains with new border checks causing tra c jammed trucks. Recently also reported, transporters delivering PPE got con scated on transportation route in transit countries. As a result, the Austrian government had to transport the equipment by air leading to enormous increase of purchasing costs. However, not only the availability but also the safety and e cacy of PPE is essential for health care workers. Recently published, a disproportional amount of masks, imported from China, failed in reliable safety testing. As a reaction to these developments Austria already started producing masks in local textile companies, especially in Vorarlberg.
Second, 35% of surveyed heads of ICUs reported shortages in more than 3 different pharmaceuticals for COVID-19 and non-COVID-19 patients.
Supply disruption of medications such as opioids, analgesics, antibiotics, and sedatives have been a global problem repeatedly during in the past decades and is increasingly affecting the EU causing widespread human misery (13). The Austrian generics producer's association (OeGV/Österreichischer Generikaverbund) reported shortages in 230 pharmaceuticals already in November 2019 (14). As recently published by our group, supply shortages may signi cantly affect quality of care with e.g. lack of remifentanil causing signi cantly longer mechanical ventilation times and consecutively signi cantly prolonged ICU stay, even under normal circumstances (15).
While Europe is one of the world's top manufacturers of drugs, the raw ingredients termed as Active pharmaceutical Ingredients (APIs) often are imported from China or India. According to the European Federation of Pharmaceutical Industries and Associations (EFPIA) as a result of rapid growth of the market and research environment in emerging economies such as China, India and Brazil during the last years, the production of APIs started to migrate from Europe to these fast-growing markets (16) (17,18). This allows countries of the western world producing cheaper generic versions of pharmaceuticals and these normally outweigh costs of transportation and custom clearance by far.
APIs are responsible for the pharmaceutical effect of formulated pharmaceuticals and are mainly produced in China (60,5%), whereas only 27,9% of global needs of APIs are produced in western Europe (18) (17). The situation aggravated under COVID-19 due to temporary lockdowns of manufacturing sites, worker quarantines, travel restrictions impacting exports, export bans, increased demand for medicines used to treat COVID-19 patient and stockpiling by hospitals, by individual citizens or at Member State level in the EU (16). Additionally, the most affected countries in the COVID-19 crisis in the EU, Italy, and Spain, are the main producers of APIs in western Europe (18). The European Commission published guidelines to ght shortages in reaction to depleted supply in many hospitals, mainly located in Austria, Italy, Sweden, Finland, and France (18) (19).
Third, in more than the half of surveyed ICU wards nurses and 68% of doctors are employed commuting from neighboring countries -especially in boarder regions-, representing a mean rate of 11,5% generally.
Di culties in crossing boarders due to travel restrictions occurred in two-thirds of Austria's critical care wards and as a result urgently needed specialized intensive care personnel is lacking.
As health care personnel is in the role of rst responders in COVID-19 pandemic, countries try to compensate staff shortage by increasing the number of medical personnel by mobilizing inactive and retired health care professionals, even if they are at higher risk of severe infection (1,20). Countries who spent a lot of Gross Domestic Product (GDP) on health expenditures, such as Switzerland, Norway and Germany have both relatively high numbers of doctors and nurses and are therefore in a more favorable situation in times of the COVID-19 pandemic. Austria has s relatively high number of doctors (approximately 5,3 per 1000 population) but low numbers of nurses (approximately 7 per 1000 population). In contrast the corresponding numbers for Germany are 4,3 doctors and 13 nurses per 1000 population respectively (20). A published study from the Austrian Ministry for Social Affairs in December 2019 reported an additional 13 000 nurses will be required in Austrian hospitals in 2030 (21). Especially staff working on ICU is extensively trained and specialized in caring for critically ill patients and operating with highly sophisticated equipment such as monitoring devices, ventilators, and extracorporeal organ support devices. Therefore, quick recruitment or training of staff from other departments or professional groups is not a viable option.

Conclusions
Summarizing the results of our survey we would like to draw attention to the lessons we can learn from the COVID-19 crisis in the EU: European Countries with Austria as a pars pro toto should establish a national production of key equipment and disposables ,at least a minor part of PPE as well as key pharmaceuticals. Secondly various stake holders of health care should undertake efforts to raise attractiveness in particular of health care professions to prevent dependency. This would not only reduce the current dependency on commuting health care personnel but eventually also compensate for the additional demand in the future. Therefore, European countries need to improve far distance supplies and invest in maintaining critical infrastructure especially in those with limited capacities such as health care in general and ICUs in particular. Although cost savings in health care systems due to reduction of beds, hospitals, and medical personnel, outsourcing pharmaceutical and PPE production seem appropriate during usual times, these apparent bene ts could easily turn into substantial disadvantages in times of crisis. Please also refer to: "In accordance with Austria's current legal situation and international guidelines, in principle, all research projects on humans must be submitted for approval to an Ethics Committee. This concerns all measures on patients and/ or study subjects, all identi able human material (e.g. blood, serum, tissue samples, DNA) or data (e.g. medical records) that are used with the purpose of obtaining knowledge and/or that do not exclusively serve the health bene ts of the patients and/or of the study subject on whom said measures are applied […]." (source: https://www.meduniwien.ac.at/web/ leadmin/content/forschung/pdf/MedUni_Wien_GSP-Richtlinien_2017.pdf ) We exclusively surveyed Intensive Care Physicians about their experiences and assessments concerning COVID-19 crisis. A verbal informed consent was obtained from surveyed heads of ICUs. We consulted the Austrian Institutional review board of Intensive Care Societies and the need of an ethic approval necessity was waved. We could provide an o cial letter of this institutional review board if necessary.

Consent for publication
Not applicable Availability of data and materials The datasets during and/or analysed during the current study available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests Funding Not applicable Authors' contributions MTL analyzed and interpreted the data regarding Austria's ICUs. CGK and GR was a major contributor in writing the manuscript. All authors read and approved the nal manuscript  Results concerning pharmaceuticals of all surveyed ICUs and in dependence of hospital type; legends: Intensive Care Unit (ICU).