Coronavirus Disease 2019 in India

India is 1 of the largest and most populated countries in the world, accounting for approximately 1.3 billion inhabitants distributed over 3,287,263 km² in both urban and rural areas, with a wide variability in access to medical care. Since the start of the coronavirus disease 2019 (COVID-19) pandemic last year, fears have been raised about the possibility of an uncontrolled spread of the virus in the country, in view of its social, demographic, and urban features. Contrary to predictions, India registered a relatively low incidence of COVID-19 cases in 2020, approximating 10,266,674 cases. Both public health measures and the national health system proved their effectiveness in containing the virus by means of lockdowns in May 2020 together with coordinated clinical management. The vaccination campaign started in January 2021, carrying with it big hopes of health and economic benefits; India being 1 of the largest manufacturers of vaccines in the world. ^{Reference Changoiwala1–Reference Rubin, Baden and Udwadia3}

The COVID-19 pandemic has progressed in India, particularly in western and northern areas, secondary to multi-factorial reasons, both virological and social, such as population density and economic migration. This has led to an incidence of approximately 350,000 cases per day in the weeks between May 1, and May 14, 2021 and a daily death toll of approximately 4000 during the same period. ^{Reference Changoiwala1–4} Moreover, rises in cases have been registered in other areas of the country, and there is also a high likelihood of under-reporting of cases and deaths. The Delta (B.1.617.2) variant, also known as the Indian variant, has recently been updated to a Variant of Concern (VOC) by the World Health Organization (WHO). ⁴

Oxygen Shortage

The current pandemic is testing the adaptability of the oxygen distribution and consumption of many countries of all sizes and economies, including India. Oxygen distribution in India, as in other countries, is mostly assured by the constant refilling of liquid O2 systems by means of tanks and cylinders. Capacity and availability of those systems is highly variable and dependent upon market, local and national policies, as well as supply chain issues, hospital facilities, transport, and logistics. Due to exceptional COVID-19-related circumstances, by mid-April 2021, many reports of oxygen shortages from different health-care facilities started to highlight the unfolding humanitarian crisis that, in a few days, would lead to an international call for help from the Indian government. The overwhelming number of new cases disrupted the health-care system and highlighted the frailty of the oxygen distribution and refilling chain. Many hospitals in the major cities of India had no more capacity to hospitalize patients and clashes and robberies targeting oxygen provisional transports and reserves were being reported. Rural areas suffered from their isolation. The price of oxygen cylinders jumped by around 9-fold, and the national government of India coordinated 1 of the biggest efforts in its history to distribute oxygen all over the country by all means, diverting the industrial oxygen supply chain toward the medical supply of oxygen. ^{5–Reference Madaan, Paul and Guleria10} Still, the situation was escalating drastically. Following the country’s request for support, the EU Civil Protection Mechanism coordinated the response agreed by EU Member States providing the shipment of oxygen, medicine, and equipment to India. It was in this context that our Emergency Medical Team (EMT)-2, based in and coordinated from Saluzzo, Piedmont Region, Italy, immediately answered the call, bearing in mind the crisis which occurred in northern Italy during the first wave of the COVID-19 pandemic in March 2020. ^{Reference Sacchetto, Raviolo and Beltrando11}

Target: the ITBP Referral Hospital

Indo-Tibetan Border Police (ITBP) is a police department with frontier duties. Among other roles, it is involved in health care and enrolls physicians from all specialties to serve the corps and communities. ITBP also has at its disposal the Referral Hospital in Greater Noida, Uttar Pradesh, India, 1 of the most affected areas of the country. ^{Reference Kumar, Vimal and Dimri12} It is a secondary care hospital with 200 beds and around 21 well-trained doctors and around 42 staff nurses. During the pandemic all hospital beds were dedicated to patients with COVID-19, with the number of medical staff increased to around 30 doctors and 64 staff nurses. At the time of our arrival, approximately 80 beds were occupied in 8 wards, located in a dedicated area of the structure, without any particular differentiation for intensity of care and/or severity of disease, due to the sudden overwhelming demand for oxygen beds. The emergency department had been closed, and patients were mainly hospitalized by referral by means of a network comprising the ITBP headquarters, Greater Noida hospitals, as well as police and hospital staff’s families and relatives. All other ordinary surgical and medical services had been suspended, as all staff (including specialists) were reallocated to care for patients with COVID-19. The radiology department was also wholly assigned to the care of patients with COVID-19, with the provision of X-ray imaging and an ultrasound system. No CT scanner was available. Intensive care unit (ICU) beds, normally located near the operating theater, were available but not active due to the lack of staff and shortages of oxygen. The hospital was running with a limited capacity of approximately 300 L/min of oxygen (18,000 L/h) and relying on a bulk cylinder system. Every hour, approximately four 46.7-L capacity cylinders were substituted by an officer assigned to that sole task. That translates to the need to substitute a cylinder weighing around 60 kg every 20 min, day and night, to ensure that a pressure of around 2 bar was reaching all patients. It was calculated that every patient would have a maximum 3 L/min at their disposal. Discussing the situation within mixed medical teams, it was highlighted that the devices providing oxygen to patients were mainly non–rebreathable-masks (NRM), oxygen delivery masks, and domiciliary B-PAP devices (ResMed™; n = 25 units). According to manufacturing standards, NRMs need between 10 and 12 L/min to maintain efficacy and reliability. On the other hand, for domiciliary B-PAP, with which an accurate FiO₂ cannot be set, resulting performance can be unpredictable. Oxygen concentrators (approximately n = 10 units), to which it was possible to connect masks, were available in the wards, each providing a maximum of around 10 L/min. Oxygen provisions were scarce and cylinders were increasingly costly and hard to obtain.

Step 1: Introduction of the Oxygen Generator to Improve the Oxygen Delivery Capacity

The main goal of our mission was to increase the total availability of oxygen from the oxygen source at the ITBP Referral Hospital. In light of previous experiences, ^{Reference Sacchetto, Raviolo and Beltrando11} the decision was made to install a Pressure Swing Adsorption (PSA) oxygen plant system (Oxygen 93 % European Pharmacopoeia 04/2011:2455) instead of relying on a cylinder or tank system. The PSA system provides a central source of oxygen generation using PSA technology (similar to concentrators) allowing the provision of 61.8 m³/h of oxygen 95% ± 1% with a pressure of 5 bar. Its main parts are shown in Figure 1 and Figure 2, and include:

Figure 1. The PSA Oxygen Plant.

Figure 2. Pictures from the field. The PSA Oxygen plant installed.

Compressor GA75 VSD+ (3-phase 400V 50 Hz); Dryer 1175 m3/h and filtration system (0.1 and 0.01 micron); Coal tower 150 and micofine filter (0.01 micron); Air tank 2000 liters; Oxygen tank 2000 liters, filter 0.01 micron and bactericidal filter; and Line reducer.

The system needs a continuous power supply of 80 kW with a starting power of approximately 200 kW. Transportation of the disassembled system (total weight, 6052 kg) was coordinated by the Italian Civil Protection Department along with the EMT-2 and was achieved thanks to the Italian Air Force C-130. After identification of an adequate site at ITBP referral hospital, the system was mounted in 36 h into a space of around 25 m². Technical and back-up tests were performed, a protective wall built, and an air conditioning system provided to maintain a steady temperature state below 25°C, as heat and humidity can affect the engine’s performance. A backup generator was also installed to assure the continuity of the system in case of electrical black-outs. The PSA oxygen plant was then connected to both the existing oxygen pipeline and the control unit at the hospital. The previous cylinder system (24 units) remained connected to the control unit as an automated pressure-regulated back-up solution in case of overflow. The pressure in the system was measured and noted (Table 1). After installation, flow meters were checked 1 by 1 to assess reliability and current usage. The pressure in the pipelines was measured on each of the wards to determine if there were any intervening leakages. Technical training about alarms and actions to put in place in case of overflow, as well as maintenance and proper use was provided both to local engineers and to dedicated staff.

Table 1. Hospital oxygen system characteristics before and after intervention

Step 2: On-Site Needs Assessment

Due to the short time available, a “go & see” approach was used. Medical and nursing teams were deployed to clinical ward rounds accompanied by local staff. Areas of interest in which interventions could potentially provide improvement in management were identified. The main areas that were targeted were clinical management (ventilation, diagnostic support, nursing, medical therapy) and organization. During ward rounds, it was noticed that early treatment was avoided due to the lack of resources (mainly oxygen delivery). Patients with SaO₂ < 90-92% were admitted and ventilation was provided with a 2-step approach. When SaO₂ levels were below 90%, NRM was the first line of treatment. With worsening respiratory distress, B-PAP was escalated. B-PAP machines were set with an inspiratory pressure of approximately 10-12 cmH₂O (IPAP) and expiratory pressure of 5 cmH2O (EPAP). All B-PAP machines were home-treatment ventilators. To ensure high flow oxygen was given to critically ill patients, the only solution was to use a second oxygen source in a very unconventional way. We also noticed that no particular differentiation in device use was applied according to the level of respiratory failure: NRMs were being used mostly for mild and moderate cases, and nasal cannula was not used. ^{Reference Graham, Bagayana and Bakare13} There was no targeted strategy of nutrition for patients with moderate and severe respiratory failure, and most of them were on peripheral parenteral nutrition. One aspect of standard treatment, remdesivir prescription, was observed for most of the admitted patients, with no differentiation made between early and late COVID-19 disease. Chest X-rays were the most used examination for diagnosis and monitoring, while no lung ultrasound (US) or ABG (arterial blood gas) exams were performed. As for the organizational side, due to scarcity of staff, there was only 1 medical doctor for nearly 90 patients in each of the 3 shifts per day. There were 5 nurses on each shift, 1 in each ward aided by 3 paramedical staff. As far as we noticed, nurses were mainly on duty for administering therapy and for patient care. No intensity of care model was used to allocate patients to different areas of the hospital, so patients on B-PAP were scattered around different wards. In the following days, a further “go & see” was required as the PSA oxygen plant was subject to several overflows due to its threshold of 1000 L/min being exceeded, mainly during night-shifts.

Step 3: Further On-Site Actions

Following the needs assessment, the following actions were implemented:

• Brief medical training with a plenary session accessible to all medical staff, attended by the vast majority, apart from those on duty.

• Ultrasound Session: a focused lung US (L-US) session was provided by 1 certified instructor. The main objectives of the session were the identification of the general characteristics of artifacts in L-US, as well as patterns, classification, progression, prognostic factors, concordance with other imaging and differentials in COVID-19-related pneumonia. ^{Reference Smargiassi, Soldati and Borghetti14} On-site practical training was available. Following on from these sessions, bed-side exams were performed during clinical rounds.

• Respiratory Failure Session: a focused respiratory failure session was provided by 2 MD specialists. The main subjects of the session were general principles, respiratory support (introducing the role of Helmet-CPAP or other devices able to provide PEEP such as Boussignac and Easyvent), devices for oxygen delivery, the role of pronation, and the rational use of oxygen flow. An on-site practical training and demonstration session was available. In line with our experience, the importance of early C-PAP treatment in moderate to severe hypoxemia was stressed. ^{Reference Bellani, Grasselli and Cecconi15,Reference Coppadoro, Benini and Fruscio16}

• Proposal for organizational changes: a diagram to better allocate patients to dedicated areas providing varying intensity of care was proposed (Figure 3). A color code was also suggested to easily define patients’ clinical profile to improve the proper use of devices and rational use of oxygen. Nasal cannulae and Venturi masks were also introduced. As per our experience, we proposed that the role of the nurses should be broadened, giving them the task of monitoring O₂ saturation and O₂ flow at least once per shift using a specific form. Another main point was on how to assist for awake pronation. To prevent oxygen plant overflow above its maximum capacity, we proposed that the hospital management and medical doctors calculate the exact number of patients treatable with different types of respiratory support according to the maximum capacity of the system (Figure 4).

• Medical Treatment Session: a focused medical treatment session was provided by 2 MD specialists. The main focuses of the session were the role of antivirals, antibiotics, immuno-modulants (especially corticosteroids) and anticoagulants and their timing during the course of the disease according to international protocols and guidelines. ¹⁷ The absence of evidence in the use of remdesivir in this setting was also discussed (Figure 5).

Figure 3. Patients’ stratification proposal according to respiratory failure during COVID-19 pandemic.

Figure 4. Different devices combination according to oxygen delivering capacity.

Figure 5. Pictures from the field. Medical therapy open session.

Short-Term Achievements

As well as achieving the main objective of our mission by increasing the oxygen availability from the hospital oxygen pipeline system from 300 L/min at 2 bar to 1000 L/min at 5 bar, the following short-term achievements were reported before the end of the mission:

• Implementation of daily morning monitoring of the number of patients on O₂ treatment, categorized by type of respiratory support;

• The opening of an 8-bed High Dependency Unit (HDU) with a dedicated nurse and 2 paramedical staff in an already existing area with ICU ventilators and monitors, made possible due to improved oxygen supply;

• The introduction of targeted oxygen therapy to achieve SaO₂ ≤ 95%, to conserve the precious oxygen resource;

• The introduction of the use of double flow fluxmeters adapting the European-manufactured connection and coupling pipes to the Indian wall entry junction, to ensure the high flow needed for Helmet-C-PAP and Easyvent mask with Ventukit. The switch from B-PAP to C-PAP, starting with Helmet and Easyvent was advised for selected patients. Optimizing oxygen use by adapting levels of assistance to changes in demand avoided the risk of overflow and hence the risk of being left with only the support of the back-up system and the breakdown of the machines. Working at nursing and ventilation support level led to the result that no more overflow was noticed in the following weeks;

• The introduction of enteral nutritional support by means of a straw through C-PAP helmets and B-PAP masks was established;

• The importance of pronation and consequent ventilation-perfusion mismatch was emphasized.

Additional Equipment Provided

The first cargo transported 20 ventilators, 1 stretcher for high-level (IV) biohazard containment, and a large amount of personal protective equipment (PPE), as well as the PSA machine along with the team. A second cargo added 2 more ultrasound machines (GE-Healthcare™), 2 ventilators (Siare Engineering™), 30 oxygen concentrators, and additional PPE.