Review

Management of COVID-19 from the pulmonologist’s perspective: a narrative review

Sanchit Kumara Department of Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Shubham Mehtaa Department of Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Nikhil Sarangdharb Lung Bulletin, Mumbai, India

Animesh Raya Department of Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaCorrespondencedoctoranimeshray@gmail.com

Sanjeev Sinhaa Department of Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Naveet Wiga Department of Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Review

Management of COVID-19 from the pulmonologist’s perspective: a narrative review

ABSTRACT

ABSTRACT

Introduction: The COVID-19 pandemic has provided global challenges to health-care facilities in ensuring the delivery of care to patients. Tremendous international collaboration has enabled the swift formulation of evidence-based guidelines that aim to clarify day-to-day issues faced by physicians and other health-care providers on the frontlines.

Areas covered: In order to provide answers to the common questions and dilemmas faced by physicians and policymakers, especially those handling pulmonary manifestations of COVID-19, the authors made a list of pertinent clinical topics that were reviewed between 21st of August, 2020 to 30th of August, 2020 by the authors using online databases that included PubMed, EBSCO, and the Cochrane Library. Literature was reviewed and included based on relevance to the topics selected. The review was aimed to serve as a quick reference for addressing practical issues faced during patient care in the ongoing pandemic with a brief account of the management of COVID-19 patients as per international guidelines.

Expert opinion: As more evidence continues to generate regarding the optimal methods of managing COVID-19 cases while caring for non-COVID patients concurrently, physicians will need to constantly reeducate themselves to keep pace with a rapidly evolving landscape of therapeutic options.

KEYWORDS:

Bronchoscopy covid-19 nebulization out-patient ppe ventilation

1. Introduction

First identified in Wuhan, China, COVID-19 rapidly evolved into a pandemic and the international and domestic numbers continue to grow [1]. Given its high infectivity, aerosol-based transmission with potential for spread by asymptomatic individuals, COVID-19 has significantly impacted the delivery of standard health-care services [2–4]. This review discusses the issues involved and summarizes the currently available evidence for the delivery of health care in the current times from the pulmonologist’s perspective.

2. Literature search methodology

A list of topics to be included in the review was prepared by the authors (SK, SM, AR) and subsequent literature search for the same was conducted on PubMed, EBSCO, and Cochrane databases from the 21st of August, 2020 till the 30th of August, 2020. Search results were reviewed for relevance pertaining to the topics and thereafter included in the final manuscript after discussion between the authors (SK, SM, AR).

3. Personal protective equipment (PPE)

PPE is classified by various agencies with regards to the level of apparent threat [5–8]. Because of the rapid increase in the number of cases necessitating an increased requirement of personal protective equipment for health-care providers (HCP), shortages have occurred and therefore, the need to optimize delivery has been addressed by various organizations such as the World Health Organization (WHO) and the Center for Disease Control (CDC) that have proposed guidelines for the rational use of PPE while taking into account the expected exposure and risk of infection [9–13].

Literature regarding infection transmission and details on the types of masks has been previously published [14,15].

A summary of the proposed PPE practices as advocated by the WHO and Indian guidelines in various scenarios is provided in Table 1 –

Table 1. Personal protective equipment in different patient settings

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3.1. Management of potential exposures

Potential exposures must be managed as per institutional and national recommendations. An example from the Indian guidelines is shown below [16]:

▪Notify the concerned authorities.

▪Assess risk:

▪Low-risk exposures are those not meeting the criteria for high risk.

▪Criteria for high risk:

▪Caring for known COVID-19 OR handling respiratory specimens from COVID-19 cases either without recommended PPE or with possible breach of PPE.

▪Aerosol-generating procedures without adequate PPE.

▪Not wearing mask/face-shield/goggles:

▪With face to face contact (within 1 m for >15 mins)

▪Accidental exposure to body fluids

▪Management [17]:

▪Low Risk: Continue to work and self-monitor for symptom development.

▪High Risk: 14 days quarantine – active symptom screening. Test if symptomatic OR between day 5 and 10 if asymptomatic.

4. Continuing routine patient services

Owing to the high rates of COVID-19 transmission, the potential for transmission by asymptomatic patients, spread through contact surfaces, and issues with the use of adequate PPE as per clinical setting, usual outpatient service sites may become potential sources of viral transmission [2,3,18–20]. For the safe handling of patients in these settings, efforts must be made to minimize transmission by [11,20–23]:

Using telemedicine to avoid patient movement and potential spread through contact. Helpline numbers must be made available so patients may know whether they need to attend a suspected Acute Respiratory Infection (ARI) clinic, conventional clinics, or whether telemedicine would suffice. Patients who cannot be managed via telemedicine maybe managed using an adapted algorithm shown in Figure 1 [23].

Figure 1. Determination of patient care site (Modified from the MoHFW Guidelines [23])

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Elective/non-urgent procedures and hospitalizations may be deferred. Increasing the duration of drug supply for chronic patients and reliance on telemedicine for reviewing and renewing prescriptions can help decrease the spread of the infection.

Unavoidable visits must be adequately planned (in advance) and patients advised against bringing contacts during visits. An algorithm to decide on the initial site of care is shown in Figure 1. Initial triage must segregate ARI cases to separate areas with staggered entry and fixed interval timings to avoid overcrowding. Patients should be screened using temperature, symptoms, rapid assays with the provision of an adequate supply of masks, at least for symptomatic and ideally for all visitors [24]. Social distancing (minimum 1 m) from other individuals must be maintained with frequent hand hygiene using alcohol-based hand rub/soap (if visibly dirty) and advising people not to touch their eyes, nose, or mouth. Cough etiquette with coughing/sneezing into bent elbow/tissue with prompt disposal of the tissue must be encouraged. Physical barriers such as glass/plastic windows or partitions must be used at areas such as the help desk, registration counters, pharmacy windows, etc. Designated personnel should be made available for COVID-19 related care for using PPE for prolonged durations.

Examination and procedure rooms must have adequate ventilation and PPE available with a single patient per room followed by the cleaning of surfaces after usage [13].

Disinfection of surfaces and rooms must follow institutional guidelines [25,26]. Ultraviolet rays, especially ultraviolet-C (UVC) have been found to be effective in inactivating the SARS-CoV2 virus [27,28]. Currently, the evidence is evolving regarding the optimal method of utilizing this modality and may provide an effective means of disinfection [29,30].

5. Patient area ventilation

The following recommendations may be considered during the operation of air cooling equipment during the current COVID-19 pandemic in inpatient and outpatient health-care facilities/hospital facilities [31]:-

Relative humidity – Maintaining this between 40% and 70% is most useful. Usually, hospitals use heating, ventilation, and air-conditioning (HVAC) systems which in ideal cases are used to maintain indoor air quality through adequate ventilation with filtration and humidification control (using humidity sensors with specified controls to regulate moisture levels) [32].

Temperature – This may be set within the range of 24–30°C as the optimally comfortable temperatures generally fall in this range after accounting for air velocity, relative humidity, and clothing [33].

Intake of fresh air/Air exchange should be ensured as much as possible while avoiding recirculation. Negative or neutral differential pressure ventilation is required for COVID areas to prevent leakage of virus-laden airborne particles outside. In health-care facilities, room AC (air conditioners) or ceiling fans are recommended with a slight opening of doors and windows further supported by exhaust fans for air replacement. It is recommended to avoid central ACs as far as possible to prevent the spread of infection.

In view of the current pandemic, health-care facilities may convert their existing patient wards and intensive care units (ICUs) into COVID wards and COVID ICU’s, respectively, with different areas earmarked for accommodating COVID-19 cases separately from suspected and non-COVID cases. Depending on the hospital infrastructure, COVID-19 positive patients can also be accommodated in Airborne Infection Isolation Rooms (AIIRs). An exhaust blower must be installed to extract the room air and exhaust it into the atmosphere after suitable treatment (given below). The supply of air quantity should provide a minimum of 12 air exchanges per hour (ACH) and a negative pressure of at least 2.5 Pa must be achieved in the room. Regular cleaning and sanitization of indoor filter units must be done.

Air Handling Units (AHUs) which are an integral part of HVAC systems may be started 2 h prior to the office time and must continue till 2 h after the office time to ensure that no contamination remains.

Exhaust Air Treatment – the exhaust air is likely to contain particles with variable viral loads, hence, suitable techniques may be used to prevent the spread of infection. This can be done via:

a.HEPA filtration (preferable method)

b.Chemical disinfection

c.Let off into the atmosphere without treatment.

6. Procedures during COVID-19

6.1. Pulmonary function testing

Pulmonary function tests (PFTs) often generate aerosols and droplets during testing and hence pose a considerable risk for the spread of infection to all patients attending pulmonary function services and the staff working there.

The following strategies may be followed to minimize the risk of transmission [31,34]:-

Referrals may be restricted to patients requiring urgent/essential tests only for immediate diagnostics of current illness (e.g. hematological malignancies before and after hematopoietic stem cell transplant, etc.). Patients with symptoms of COVID-19 or flu-like symptoms should not be tested at this time. Routine testing must be postponed. COVID-19 patients may not be tested for at least 30 days after infection or resolution of clinical symptoms with 2 negative RT-PCR tests on nasopharyngeal and throat swabs separated at least 24 h apart.

Waiting areas should be reorganized and infection prevention strategies based on local institutional guidelines should be instituted. Immunocompromised patients should be scheduled for testing at the start of the day, before other patients arrive, whereas potentially infected patients should be scheduled for testing at the end of the day to prevent cross-infection.

Testing should be limited to spirometry and diffusion capacity of carbon monoxide (CO) carried out with a high specification, disposable, in-line bacterial, and viral filter in place. Disposable-combined mouthpieces/sensors can be used if an additional filter can be added to the patient circuit which would not affect the measurements.

Exercise testing, nebulization, bronchial challenge tests, and other aerosol-generating procedures should be postponed. Pressurized metered-dose inhaler (pMDI) via a spacer should be preferred over nebulization for the administration of any drug. Spacers should not be shared between patients.

Mouthpieces, filters, nose clips, and sensors have a high risk of contamination since they come in direct contact with the patient, hence, should be replaced after every use to minimize the risk of cross-infection. Adequate PPE in this setting includes N95/FFP2 masks and eye protection (goggles or face shield).

The testing space and equipment should be cleaned with chlorine solutions at a concentration of 1000 ppm or with polyphenol solution at a concentration of 1%, according to the manufacturer’s indications. Routine cleaning of floors with detergent and water is recommended.

In the post – peak phase of the disease, when the pretest probability of infection is lower than in the pandemic phase, all testing procedures including exercise testing, nebulization, bronchial challenge tests, whole-body plethysmography, and other aerosol-generating procedures can be reintroduced with extra precautions (Full PPE and appropriate N95 Mask)

6.2. Bronchoscopy

Patients infected with SARS-CoV-2, whether symptomatic or not, can transmit the virus to other individuals. Given that the virus could be transmitted via droplets and aerosols along with indirect spread via fomites, open airway procedures such as bronchoscopy pose a significant risk to health-care workers (HCWs), both during coughing and transmission by fine droplets and aerosols [35]. The evidence on the role of bronchoscopy during the COVID-19 pandemic is, however, sparse. To maximize protection of patients and HCWs, the following recommendations may be considered in view of the current COVID – 19 pandemic while at the same time understanding that these are mostly based on expert opinion and/or consensus only [36]:

Bronchoscopy may be considered only for urgent indications such as massive hemoptysis, foreign body aspiration, mucus plug leading to collapse, severe or symptomatic tracheal or bronchial stenosis, diagnosis of lung mass suspicious of cancer, and mediastinal or hilar lymphadenopathy suspicious of malignancy. Elective indications such as chronic cough, asymptomatic tracheal stenosis, etc., should be delayed.

As bronchoscopy has limited diagnostic utility in COVID-19, samples via nasopharyngeal and oropharyngeal swabs may be preferred [37]. In intubated patients, specimens can include tracheal aspirates and non-bronchoscopic alveolar lavage (Mini-BAL).

In areas with community transmission, health-care workers in bronchoscopy suites should use an N-95 respirator or a powered air-purifying respirator (if available), gown, gloves, and cap [38]. Where community spread is not present, such precautions must be followed only for patients with suspected or confirmed COVID-19 infection with standard precautions in other cases.

In areas with community transmission, wherever feasible, even asymptomatic patients may be screened prior to the procedure.

Regional availability of diagnostic and therapeutic interventions should be considered, particularly in resource-depleted (resource-constrained) hospitals to prioritize availability.

In patients with confirmed COVID-19 infection who recover and need a routine bronchoscopy, evidence suggesting the appropriate timing of the procedure is lacking. However, as per expert recommendations, it is recommended to wait at least 30 days from resolution of symptoms with negative SARS-CoV-2 RT-PCR tests from at least two consecutive nasopharyngeal swab specimens collected 24 h apart.

When available, a single-use disposable flexible bronchoscope should be preferred to a standard re-usable fibreoptic bronchoscope as less equipment is involved in the set-up, post-procedure disinfection, and transport [39]. While doing bronchoscopy in an intubated patient, the patient should not be disconnected from the ventilator to avoid contamination and closed-circuit ventilation should be maintained [40]. This can be done by means of an adapted valve that facilitates the introduction of the bronchoscope into the airway without disconnection of mechanical ventilation. Intubation of patients via bronchoscopy should be avoided, as there is an increased risk of contamination due to aerosolization.

The disinfection of endoscopes may be done in the usual way as per local guidelines. The cleaning of surfaces likely to have been soiled such as armchair, stretchers, tables, devices, and floors must be carried out as per local institutional guidelines [41].

6.3. Nebulization

A number of inhaled medications needs to be regularly used for patients with diseases such as asthma, bronchiectasis, and COPD including corticosteroids, antibiotics, and bronchodilators. Administration of nebulization therapy produces aerosols that are potentially infectious, with a risk of transmission [2]. A study involving a confirmed COVID patient failed to show any RNA in the air samples obtained from 10 cm around the patient’s chin both with and without the use of a surgical mask while breathing quietly, breathing deeply, and coughing inside an airborne infection isolation room [42].

Some country-specific guideline list nebulizers as a low-risk procedure with a rationale that the aerosol is not derived from the patient’s respiratory tract but rather the nebulizer machine itself [43,44]. However, as the transmission from close-range viral aerosol generation is still possible, steps must be taken to minimize risk to health-care workers (HCWs) which include [35,45–47]-

Change to metered-dose inhalers (MDIs) or dry powder inhalers wherever possible. The MDIs should be used with dedicated spacers and valved-holding chambers.

Use high-efficiency particular air filters (HEPA) with the nebulizers to minimize the risk of transmission with the use of filters/one-way valves on the tubing of jet nebulizers and adding filters to the end of the mouthpiece while avoiding face masks as the delivery interface.

HCWs must use adequate PPE (face masks, goggles, gloves, and gowns) while setting up nebulizers and if possible close the patient room door and wait outside after treatment is initiated.

For mechanically ventilated patients, a jet nebulizer or pMDIs should be avoided due to the breakage of the circuit required for the placement of the devices. Preferentially, mesh nebulizer must be used as their design allows the medication to be added without breakage of the circuit, it is isolated from the breathing circuit and they can be kept in place for up to 28 days. HEPA filters must be attached to the expiratory limb of the ventilator to reduce aerosol generation.

Aerosol therapy should not be used along with pulmonary clearance techniques such as suctioning or chest physical therapy because of the increased chance of transmission. In-line or closed system suction systems must be used, and personnel must don adequate PPE – N95, gown, goggles/face shield, and double gloves.

7. Management of chronic lung diseases

7.1. Asthma

As per current evidence, asthma does not appear to be a strong risk factor for acquiring COVID – 19 infection, although poorly controlled/uncontrolled asthma may lead to a more complicated disease course for those patients infected with COVID-19 [48,49]. Expert recommendations suggest that all regular medications necessary to maintain asthma control, including inhaled glucocorticoids and/or oral glucocorticoids may be continued during the COVID-19 pandemic as maintaining good asthma control helps minimize the risk of an asthma exacerbation [50]. The usual guidelines for prompt initiation of systemic glucocorticoids for asthma exacerbations should be followed, as delaying therapy can increase the risk of a life-threatening exacerbation [51]. Inhaled glucocorticoids used for asthma have not been found to have an adverse effect on the course of COVID-19 infection [52,53]. In case the patient is already on oral steroids as controller therapy, low-dose dexamethasone should not be used in severely ill COVID – 19 patients. Inhaled medications should be given by inhaler rather than nebulizer for patients with COVID-19 infection to avoid aerosolizing the virus and enhancing disease spread [35,51].

7.2. Chronic obstructive pulmonary disease

Expert recommendations suggest that all maintenance medications necessary to maintain control of COPD and prevent exacerbation, including inhaled glucocorticoids, should be continued during the COVID-19 pandemic [54,55]. Individuals with COPD should try as much as possible to avoid COVID-19 exposure using hand hygiene and social distancing. Like in asthma, evidence regarding inhaled glucocorticoids having an adverse effect on the course of COVID-19 is lacking. Like the usual protocol, systemic glucocorticoids must be initiated as soon as possible during a COPD exacerbation. For patients hospitalized with COVID-19, the use of nebulized medications should be avoided and metered-dose inhalers (MDI) must be used because of the risk of aerosolizing SARS-CoV-2 and enhancing disease spread. MDI with spacers can also be used.

7.3. Interstitial lung diseases

Prednisone, mycophenolate mofetil, azathioprine, cyclophosphamide, and rituximab are immunomodulatory medications often used to treat ILD. Immunosuppressed patients do not appear to have an increased risk for COVID – 19 or have severe COVID-19 infection with respect to the normal population; however, limited data exists regarding the initiation or maintenance of immunomodulatory therapies for patients with fibrotic ILD during the COVID-19 pandemic [56]. Expert recommendations suggest that patients with progressive disease should typically be offered immunomodulatory therapy, preferably steroid – sparing agents, wherever possible – for patients already receiving immunomodulatory therapy, recommendations suggest maintaining patients on at least low doses of immunomodulatory therapy, again prioritizing steroid-sparing medications over prednisone [57]. Early or rapid taper of therapy is strongly discouraged, since it may lead to disease flare. In acute exacerbations of ILD, steroids may be considered in cases more likely to respond to steroids, such as ILD related to exacerbation of underlying connective tissue disease; however, limited data exists in view of the current COVID pandemic [58].

8. COVID-19 care

A majority of infected individuals (81%) have mild symptoms while severe cases (dyspnea, hypoxia, or >50% lung involvement on imaging) account for 14% of cases and 5% of cases are critically ill (respiratory failure, shock, or multiorgan dysfunction). Patients develop dyspnea at a median of 5–8 days after symptom onset while ARDS develops 8–12 days after symptom onset with hospitalization occurring around 10–12 days with hospitalization lasting 10–13 days for survivors [59]. A stepwise approach to such cases is presented below.

8.1. Imaging in suspected cases

Lower respiratory tract involvement with COVID-19 produces radiographic abnormalities that may provide clues to the diagnosis and help in the assessment of severity. The performance of various imaging modalities is summarized in Table 2-

Table 2. Imaging modalities for COVID-19

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Chest imaging should NOT be used for diagnosis of COVID-19 unless RT-PCR is unavailable, RT-PCR results are delayed or initial RT-PCR is negative with a high index of clinical suspicion [60]. Imaging can help decide on the level of care for suspected/confirmed cases but discharge decisions must be based on clinical and laboratory data rather than imaging [60].

These appearances can be used within suggested pathways that integrate radiological assessment in the evaluation of suspected COVID-19. Such an example using a modification of the algorithm described by the BTSI is shown below in Figure 2 [61].

Figure 2. Algorithm for imaging in suspected COVID-19 cases (modified from the British Thoracic Society for Imaging [61])

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8.2. Methods of testing

Suspected cases are defined by the WHO as those with an epidemiological link to COVID-19 and symptoms (fever and cough or ≥3 of fever, cough, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, anorexia/nausea/vomiting, diarrhea, altered mental status) [62]. These are ideally sampled using nasopharyngeal and oropharyngeal swabs with lower respiratory sampling reserved for more advanced cases or where upper respiratory sampling has been negative but there is still strong clinical suspicion [63].

The WHO advocates using nucleic acid amplification tests (NAATs) at the start, with repeat testing reserved for cases testing negative but still having a high clinical suspicion of COVID-19 [63]. For centers with unavailability or long turn-around times for NAATs, rapid antigen tests may be used if ≥80% sensitivity and ≥97% specificity compared to NAATs. In such cases, positive tests are interpreted as COVID-19 cases while negative cases may undergo further testing if clinically suspected [64].

8.3. Stratification of severity, site of care and prognostication

The management of COVID-19 starts with clinical stratification of patients to identify those with poor prognostic factors or a deteriorating clinical profile that warrants admission. The CDC/NIH divides this as follows [70, 118]:

Mild Illness: Signs and symptoms of COVID 19 including fever, cough, sore throat, malaise, headache, muscle pain without shortness of breath, dyspnea, or abnormal chest imaging. These patients are managed in the ambulatory setting/home-based care with telemedicine follow-up.

Moderate Illness: Patients with evidence of lower respiratory disease by clinical or radiological assessment with the saturation of oxygen (SpO2) ≥94% on room air at sea level. Close monitoring of clinical and laboratory parameters is required in these cases and admission maybe needed.

Severe Illness: Patients with tachypnea (rate >30/min, SpO2 <94% on room air, the ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg or lung infiltrates >50%). These patients are preferably admitted to Airborne-Infection-Isolation-Rooms and may require ICU admission.

Critical Illness: Patients with respiratory failure, septic shock, and/or multiple organ dysfunction. These patients must be managed in the ICU.

Prognostication: The 4 C Mortality Score provides an easy to use score-predicting mortality at the time of admission using common clinical (age, sex, no. of comorbidities, respiratory rate, peripheral oxygen saturation, Glasgow Coma Scale), and laboratory parameters (urea, C-reactive protein) that are usually available in the first few days after admission [65]. It compares favorably against similar scores and provides the convenience of use which has been externally validated [66]. The WHO recommends using National Early Warning Score 2 (NEWS2) and Pediatric Early Warning Score (PEWS) which uses clinical parameters to predict the requirement for more stringent monitoring and escalation of the level of care [67].

8.4. Management of hypoxia

8.4.1. High-flow nasal cannula (HFNC)

During the COVID-19 pandemic, high-flow nasal cannula (HFNC) has emerged as an attractive option to reduce the intubation rate and improve the clinical prognosis in patients of COVID-19 with acute respiratory failure. Its benefits include high rates of tolerance, the ability to deliver aerosolized medications, and use in conjunction with awake proning [68]. However, the potential for aerosol generation and transmission of infection is not well defined [69]. Most guidelines allow for HFNC use under careful monitoring, especially when used with risk mitigation strategies such as patient masks and PPE use [68–71]. A ROX index (ratio of oxygen saturation via pulse oximetry/FiO2 to respiratory rate) <2.85 at 2 h, <3.47 at 6 h, and <3.85 at 12 h of HFNC initiation predicts HFNC failure [72].

8.4.2. Noninvasive ventilation

NIV can provide crucial support to patients with respiratory failure by reducing work of breathing, recruiting atelectatic alveoli, delivering high oxygen concentrations, and the ability to deliver nebulized medications during use. However, issues pertaining to viral aerosol generation, intolerance, development of pressure sores, and worsening hemodynamics in patients with shock require consideration prior to use [68]. Guidelines allow the use of NIV under careful monitoring, especially when HFNCs are not readily available [70,71].

8.4.3. Invasive mechanical ventilation

Despite treatment, a small fraction of infected cases will eventually develop worsening hypoxemia that would necessitate intubation. The guidance regarding the procedure specific to COVID-19 pertains to adequate pre-oxygenation for 5 min using 100% oxygen, use of rapid sequence intubation, aerosol reduction by avoiding bag-mask ventilation or use with filters if necessary and ensuring high first-pass success rates with experienced operators, and use of video laryngoscopy/bougies [70,73].

Ventilator setup must aim for oxygen saturation >90% in patients (>88% for those with COPD) [74]. Optimal PEEP and FiO2 settings for COVID-19 tend to favor high PEEP settings with careful monitoring for a response but the description of the H (high elastance and lung weight, high recruit ability, shunt physiology predominant) and L phenotypes (low elastance and lung weight, low recruit ability, VQ mismatch predominant) of hypoxia may enable the more educated application of recruitment maneuvers and ventilation mode selection [70,71,74,75]. Prone ventilation, use of neuromuscular blockade, and pulmonary vasodilators maybe used as additional strategies on an individual basis [71,74].

8.4.4. Extra-corporeal membrane oxygenation (ECMO)

Veno-venous ECMO has been advocated for use in patients with COVID-19 who develop refractory hypoxemia defined as a PaO2/FiO2 ratio of <60 for >6 h, <50 for >3 h, or pH <7.2 with pCO2 >80 mm Hg for >8 h despite optimal ventilatory management that includes protective lung ventilation with adequate positive end-expiratory pressure (PEEP), prone ventilation, neuromuscular blockade, and consideration for recruitment maneuvers/vasodilators. Indications for veno-arterial ECMO includes a co-existent need for hemodynamic support for cases with cardiogenic shock [76]. While clinical data regarding real-world use are still evolving, limitations are imposed by inadequate resources and access to experienced ECMO centers. Early registry data show favorable outcomes with early institution of ECMO support [77].

8.5. Specific medications

While many investigational drugs are being tried for the treatment, a few modalities have been found to be beneficial and the approved therapies so far are summarized in Table 3.

Table 3. Guidelines for approved therapies in COVID-19

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8.5.1. Steroids

The pathophysiology of severe COVID-19 involves excessive immune activation causing organ dysfunction [78,79]. Therapeutic modalities with anti-inflammatory properties were therefore considered for use to improve outcomes in patients with severe disease [79].

Early studies had indicated that the use of methylprednisolone in patients with COVID-19 related ARDS resulted in reduced mortality, reduction in clinical worsening, earlier defervescence, and faster improvement of radiological appearance without adversely affecting viral clearance [80–83].

This was subsequently tested directly in the multi-center, randomized, controlled, open-label RECOVERY trial [84]. Analysis from the arms comparing the use of dexamethasone 6 mg once daily for up to 10 days vs usual care showed a significantly reduced age-adjusted rate ratio for mortality in the dexamethasone vs usual care arms of 0.83 (95% CI 0.74 to 0.92, p < 0.001). This effect was seen in those receiving invasive mechanical ventilation or supplemental oxygen [85].

8.5.2. Remdesivir

Remdesivir is an inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase [86]. Preliminary report of a multinational, randomized placebo-controlled trial in 1059 patients with COVID – 19 by Beigel JH et al., concluded that remdesivir led to faster time to recovery (discharge/continued hospitalization without need for supplemental oxygen) (median 11 versus 15 days with placebo). A trend toward lower 14-day mortality was not statistically significant (7.1 versus 11.9% with placebo) overall but became statistically significant (2.5 versus 11%) in the subset requiring oxygen supplementation but not noninvasive or invasive ventilation [87].

Based on available data, remdesivir was recommended by the FDA via Emergency Use Authorization (EUA) for severe COVID–19 as defined by SpO2 ≤94% on room air, requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation [ECMO].

This is to be administered 200 mg intravenously on day 1 followed by 100 mg daily for 10 days total in patients on mechanical ventilation or ECMO and 5 days total in other patients (with extension to 10 days if there is no clinical improvement).

Contraindications include alanine aminotransferase ≥5 times the upper limit of normal and/or estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m². This must not be used with hydroxychloroquine because of potential drug interactions [88].

8.5.3. Anticoagulants

COVID-19 infection has been found to be a procoagulant state with evidence of complement and neutrophils extracellular traps mediated endothelial injury [89,90]. Studies have even shown a direct cytopathic effect in endothelial cells after ACE2R mediated cellular entry [91]. This, coupled with immobilization in the critically ill, brings together a multitude of factors that increases the risk of thromboses.

A meta-analysis showed that the overall incidence of thrombosis in COVID-19 patients was 12.2% (CI 10.7–13.8%) which increase to 27% (95% CI 23.8–30.4%) for studies with >75% ICU patients [92]. The same was reflected in the published autopsy series that revealed the presence of thrombi in multiple organs including the lungs in patients who had died of COVID-19 [93,94].

Abnormal coagulation parameters (increased D-dimer, thrombocytopenia, prolonged PT, and elevated fibrinogen – ‘COVID-Associated-Coagulopathy’) and a higher incidence of disseminated intravascular coagulation were also found to be associated with increased mortality [95–98]. In attempting to understand whether anticoagulation might improve outcomes, a retrospective analysis of 449 patients with severe COVID-19 infection showed that the 28-day mortality was reduced in patients with SIC score ≥4 (40.0% vs 64.2%, P = .029), or D-dimer >6-fold of upper limit of normal (32.8% vs 52.4%, P = .017) [97,99].

Subsequently, anticoagulation has been recommended by most professional organizations and its use is summarized in Table 3 [100–102].

8.5.4. Prophylactic antibiotics

Guidelines for usage of empirical antibiotics in COVID-19 patients varies with regards to factors such as the local epidemiology, severity of presentation, availability of point-of-care testing respiratory pathogen panels, and antimicrobial stewardship programs. Compared to influenza, superadded bacterial infections do not seem to be as common, and international guidelines including those from the CDC and WHO do not recommend routine usage of antibiotics in COVID-19 cases although some country-specific guidelines advocates use in cases of severe infection, sepsis or shock, with clinical suspicion of a concurrent bacterial infection or atypical radiological features [103]. Institution specific decisions, especially when combined with regular data audits and an antimicrobial stewardship program should provide the best way to formulate institutional policies regarding the same.

8.5.5. Antipyretics

Although there were initial concerns regarding adverse outcomes with the use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19 patients, more data have not shown the same and prompted international agencies to allow management of fever in COVID-19 patients with agents such as acetaminophen and if needed, lowest effective doses of NSAIDs like ibuprofen [104–106].

8.5.6. Other drugs

Apart from the drugs mentioned above, many experimental drugs are being tried for the management of COVID-19 infection. The efficacy of these drugs remains uncertain and the current recommendations regarding their use are summarized in Table 4 .

Table 4. Use of experimental therapies in COVID-19

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8.6. Monitoring COVID-19 patients

Hospitalized patients require close clinical monitoring to detect early signs of worsening. The WHO recommends the use of early warning scores such as the National Early Warning Score 2 (NEWS2) and Pediatric Early Warning Score (PEWS) that use clinical parameters to help decisions regarding the level of care and frequency of monitoring [67]. It may be reasonable to obtain routine blood counts, electrolytes, renal, and liver function tests with consideration of specific tests such as D-dimer, aPTT, LDH, CRP, IL-6, procalcitonin, blood, or sputum cultures for prognostication and cases with diagnostic uncertainty. A number of extra-pulmonary manifestations maybe associated with COVID-19 infection and literature regarding these has been previously published [107].

8.7. Cardio-pulmonary resuscitation

Cardiopulmonary resuscitation in COVID-19 patients poses a high risk of viral transmission related to aerosol-generating procedures, high-stress scenarios, and multiple operators in the resuscitation team. Guidance for reduction of risk in these situations includes donning adequate PPE prior to entering the patient area, limiting the number of providers to only essential members during resuscitation, use of mechanical CPR devices, and use of HEPA filters during ventilation with minimization of closed-circuit disconnections. Airway management must include consideration of early intubation with a cuffed tube by the incubator with the most experience and consideration of video laryngoscopes to decrease aerosol exposure. Adjuncts such as passive oxygenation using non-rebreathing masks maybe used for short durations with consideration for supraglottic devices if intubation is delayed [108].

9. Conclusion

The SARS-CoV-2 pandemic has provided numerous challenges in the management of both COVID-19 and non-COVID-19 cases in health-care setups. Rapidly evolving literature has helped chart a way forward in these uncertain times. Staying abreast with updated recommendations and employing strict infection control practices can help in slowly and safely resuming usual health-care services while optimizing outcomes for those suffering from COVID-19.

10. Expert opinion

The COVID-19 pandemic has caused an unprecedented surge in health care around the world. Numerous challenges are being faced from the limitation in ventilator numbers to shortages of the trained workforce needed to manage them. A rapidly expanding pool of literature has spurred the formulation of guiding principles based on the transmission characteristics and natural history of the infection with the novel coronavirus.

International agencies have come forth with guidance on the appropriate use of protective equipment in different settings to ensure availability in the areas that need them most. This combined with recommendations for universal public masking has served to reduce the exponential growth of new cases. This growth has had a major impact on health-care setups that have found themselves struggling to find the optimal balance in continuing delivery of services to the local populations while ensuring safe handling of suspected and confirmed COVID-19 cases at the same time. Use of telemedicine, implementation of strict infection control measures, and continued reinforcement of hand hygiene, cough etiquette, and social distancing has been found to be successful. The low cost of these interventions balanced against the huge expenses of potential cases justifies an aggressive pursuit of prevention and containment measures.

While initial experience in dealing with the disease came from extrapolation of data from cases with influenza, severe acute respiratory syndrome (SARS), and the lessons learned through the decades in the management of ARDS, a series of pertinent trials subsequently answered questions pertaining to the use of remdesivir and role of steroids in reducing mortality. These two important lessons – use of antiviral medications early in the course reduce viral turnover and that the addition of immunosuppression at the time of onset of hypoxia resulting from inflammation reduces mortality has been instrumental in providing optimal care of patients that develop moderate and severe illness. The findings of a pro-thrombotic state with severe COVID-19 infection and improved outcomes with the use of anticoagulants further strengthened the armamentarium against the pandemic. As literature continues to evolve, trials would need to establish the efficacy of individual drugs and demonstrate a favorable interaction profile with other approved therapies to be useful for guiding routine patient management. While local practices may advocate the use of drugs that may theoretically benefit COVID-19 patients, these too must be rigorously studied for efficacy before being accepted as parts of national strategies.

Despite these measures, some patients will still develop hypoxemia and we now have HFNCs and NIV which can be used with self-proning as means of avoiding invasive ventilation under close monitoring. While good rationale underlies the utilization of these measures, data is still scarce regarding the exact implementation strategies that can improve outcomes. Usage of these measures should, however, not delay intubation when the indications arise. Optimal ventilator strategies for mechanically ventilated patients remain under study with early descriptions of a dynamic spectrum between an H and L phenotype that may enable decisions regarding the optimal use of positive end-expiratory pressure and oxygen concentrations. Once again, these observations of clinical behavior and logical extrapolations to management strategies must require testing under-controlled settings to establish the utility of such measures. Till more robust evidence can help make more informed decisions, institutional guidelines should be formulated and applied systematically to provide an adequate level of care with ongoing monitoring and feedback to strengthen management pathways.

As more is learned about the clinical behavior of COVID-19, strategies will continue to be refined and physicians must keep themselves abreast with rapidly evolving literature to continue expanding their armamentarium with clinically proven therapies against the unprecedented pandemic that has caught the world grossly unprepared. Unwavering commitment and resilience will hopefully allow mankind to once again emerge victorious.

Table 1. Personal protective equipment in different patient settings

Setting	Activity	Risk	Mask	Gloves	Goggles	Face-shield	Coveralls	Remarks	References
Doctor's chamber	Clinical management	Mild	Triple layer	Yes	-	-	-	No aerosol generating procedures should be allowed.
Chamber of Dental/Otorhinolaryngologist doctors/Ophthalmology doctors	Clinical management	Moderate	N95	Yes	Yes	Yes	–	Aerosol generating procedures anticipated. Face shield, when a splash of body fluid is expected
Pre-anesthetic checkup (PAC) clinic	PAC	Moderate	N95	Yes	Yes*	-		* Only recommended when close examination of oral cavity/dentures is to be done	[13,15]
Ward/patient rooms	Clinical management	Mild	Triple layer	Yes	-	-	-	Stable patients, no aerosol generation
Intensive care units (ICU)/critically ill	Critical care	Moderate	N95	Yes	Yes	Yes	-	Aerosol generation ±. Face shield when body fluid splashes expected
Ward/ICU/other	Body packing/transport	Low	Triple layer	Yes	-	-	-	-
Emergency	Attending emergency cases	Mild	Triple layer	Yes	-	-	-	No aerosol generation
	Severely ill, aerosol generation	High	N95	Yes	Yes	-	Yes	-
COVID-19 areas	Direct care, without aerosol generation	Moderate	Triple layer	Yes	Yes (or face-shield)	Yes (or goggles)	Yes	-
	Direct care, aerosol generation	High	N95	Yes	Yes	Yes	Yes	-

Table 2. Imaging modalities for COVID-19

Modality	Typical Findings	Sensitivity	Specificity	Limitations	References
Chest x-ray	Classic/Probable COVID-19: Lower lobe and peripheral predominant multiple opacities that are bilateral (≫ unilateral)	25–69%	Up to 90%	Limited sensitivity	[109–112]
	Indeterminate for COVID-19: Not fitting classic/non-COVID-19 descriptors
	Non-COVID-19: Pneumothorax/Lobar pneumonia/Pleural effusion(s)/Pulmonary oedema/Other
Chest CT	Classic/Probable COVID-19: Bilateral, basal, GGO/Crazy-Paving/Peripheral consolidation/Reverse halo/Perilobular pattern	91–96%	26–50%	Relatively higher radiation dose Logistical issues with serial assessment Limited bedside availability Nosocomial transmission risk	[61,113–117]
	Indeterminate for COVID-19: Non-peripheral GGO/Complex/Unilateral/Other
	Non-COVID-19: Lobar pneumonia/cavitation/tree-in-bud/centrilobular nodules/lymphadenopathy/effusions/other patterns
Ultrasound	Posterior and inferior lung field involvement Large no. of B lines (‘waterfall or light beam sign’), consolidations (C-profile) Pleural line abnormalities with or without subpleural consolidations/localized pleural effusions	77–100%	79–83%	Operator dependent Requires close proximity to the patient Availability issues	[117–122]

CT: Computerized tomography, GGO: Ground glass opacity

Table 3. Guidelines for approved therapies in COVID-19

Agency	Therapy	Population	Agent and route	Dose	Duration	References
NIH	Anticoagulation	All hospitalized COVID-19 patients as per standard of care for other patients unless contraindicated	LMWH and UFH maybe preferred in hospitalized, critically ill	Not specified	Not specified	[123]
	Remdesivir	Requiring supplemental oxygen OR SpO2 <94% on room air Mechanical ventilation or ECMO	IV Remdesivir	200 mg on Day 1, then 100 mg OD	5–10 days	[124]
	Steroids	Adult COVID-19 patients: requiring supplemental oxygen OR mechanical ventilation	Dexamethasone (including pregnant women)	6 mg/day	Up to 10 days	[125]
NHS	Remdesivir	>12 years of age with: Pneumonia requiring supplemental oxygen eGFR≥30/min/m2 ALT <5 ULN	IV Remdesivir	200 mg on Day 1, then 100 mg OD	5–10 days	[126]
	Steroids	Adults hospitalized with COVID-19 requiring oxygen, mechanical ventilation or ECMO.	Dexamethasone – IV or Oral	6 mg/day	Up to 10 days	[127,128]
	Steroids		If Pregnant/breastfeeding - Oral prednisolone OR IV hydrocortisone	40 mg/day 80 mg twice a day	Up to 10 days
Ministry of Health and Family Welfare, India	Anticoagulation	Mild COVID-19: No criteria for moderate/severe	Not recommended	-	-	[129]
		Moderate COVID-19: SpO2 <94% on room air OR RR > 24/min WITHOUT contraindication/high bleeding risk	Inj. Enoxaparin, SC	40 mg OD	Not defined
			Inj. UFH IV	Not defined	Not defined
		Severe COVID-19: Respiratory distress requiring mechanical ventilation (invasive OR noninvasive) OR RR ≥30/min, SpO2 <90% on room air WITHOUT contraindication/high bleeding risk	Inj. Enoxaparin SC OR	40 mg BD	Not defined
			Inj. UFH IV	Not defined	Not defined
	Remdesivir	Mild COVID-19	Not recommended	-	-
	Remdesivir	Moderate disease (on supplemental oxygen) provided: eGFR>30 ml/min/m2 Age >12 years AST/ALT <5 ULN No pregnancy/lactation	Investigational use - IV Remdesivir	200 mg Day 1, then 100 mg	5 days
	Steroids	Mild COVID-19:	Not recommended	-	-
		Moderate COVID-19:	IV Methylprednisolone	0.5–1 mg/kg/d	3 days
		Moderate COVID-19:	Dexamethasone	0.1–0.2 mg/kg/d	3 days
		Severe COVID-19:	IV Methylprednisolone	1–2 mg/kg/d	5–7 days
		Severe COVID-19:	Dexamethasone	0.2–0.4 mg/kg/d	5–7 days
Italian Society of Infectious and Tropical Diseases	Remdesivir	Need for oxygen therapy or rapid clinical deterioration Severe pneumonia, ARDS or respiratory failure, hemodynamic instability, need for mechanical/noninvasive ventilation	IV Remdesivir	200 mg loading, then 100 mg OD	10 days	[130]
	Steroids	Brescia COVID Respiratory Severity Score ≥2 OR ARDS after 24 h of diagnosis	Dexamethasone	20 mg/day for 5 days, then 10 mg/day	Total 10 days	[130]

ALT: Alanine transaminase, ARDS: Acute respiratory distress syndrome, BD: Twice a day, ECMO: Extra-corporeal membrane oxygenation, eGFR: Estimated glomerular filtration rate, Inj.: Injection, IV: Intravenous, LMWH: Low molecular weight heparin, OD: Once daily, SC: Subcutaneous, UFH: Unfractionated heparin, ULN: Upper limit of normal

Table 4. Use of experimental therapies in COVID-19

Drug	Population	Dosage	Guidelines				References
Drug	Population	Dosage	NIH	WHO	NHS	MoHFW	[70,129]
Favipiravir	Mild to moderate COVID-19 infection	Tablet favipiravir 1800 mg twice on Day 1, then 800 mg twice a day up to day 14	-	Not outside clinical trials	-	DCGI approved for emergency use	[131–134]
Tocilizumab	Moderate disease (SpO2 90–94% on room air OR RR >24/min) with progressively increasing oxygen requirements OR mechanically ventilated patients not improving despite use of steroids	IV: 8 mg/kg (maximum 800 mg at one time); dose can be repeated once after 12 to 24 h if needed	No recommendation for or against	Not outside clinical trials	-	Off label maybe used for refractory cases	[79,123,132,p.]
Vitamin C	Adults >18 years of age with COVID-19 including those with severe infection	Tablet Vit. C 500 mg once to twice/day, IV Vit. C 12 g BD x 7 days	No recommendation for or against	-	-	-	[133,135–137]
Zinc	Hospitalized patients with COVID-19 receiving either hydroxychloroquine or azithromycin [138]	Tablet zinc sulfate – 220 mg BD x 5 days	Recommends against the use of zinc above the recommended dietary allowance	-	-	-	[138]
Ivermectin	Patients diagnosed with COVID −19 infection (hospitalized as well as outpatient ambulatory care)	Tablet 600 ug/kg x 5 days OR 1200 ug/kg x 5 days (as a part of clinical trial)	-	-	-	-	[139]
Hydroxychloroquine	Mild and moderate COVID-19 (RR>24, SpO2 <94% on room air) provided QTc <500 msec	Tablet HCQ 400 mg BD on day 1 f/b 200 mg BD till Day 5	Recommendation AGAINST use	NOT recommended outside clinical trials	-	Maybe used for mild and moderate cases	[129,140]
Azithromycin	Patients diagnosed with COVID −19 infection (hospitalized as well as outpatient ambulatory care)	Azithromycin – 500 mg on day 1 followed by 250 mg OD x 4 days along with hydroxychloroquine	Recommends against the use of the combination, except in clinical trials	-	-	-	[141,142]

BD: Twice a day, DCGI: Drug Controller General of India, IV: Intravenous, MoHFW: Ministry of Health and Family Welfare, NHS: National Health Service, NIH: National Institute of Health, RR: Respiratory rate, SpO2: Pulse oximetry, WHO: World Health Organization

Disclosure statement

No, potential conflict of interest was reported by the author(s).

Article highlights

•COVID-19 infection has created unique challenges in the delivery of health care populations.
•Evidence-based practice guidelines are rapidly being updated to provide suggestions regarding the best practices in the current times.
•There is an urgent need for change in the modes of health-care delivery with emphasis on strict infection control at all levels to minimize the risk of transmission.
•Care of non-COVID patients can continue while minimizing disruptions by observing adequate precautions.
•Systemic corticosteroids, anticoagulants, and remdesivir have been added to the available armamentarium against COVID-19 with an improvement in outcomes.

Declaration of interest

The authors declare that this paper was not funded or sponsored by any agency. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Expert Review of Respiratory Medicine

Management of COVID-19 from the pulmonologist’s perspective: a narrative review

Review

Management of COVID-19 from the pulmonologist’s perspective: a narrative review

ABSTRACT

1. Introduction

2. Literature search methodology

3. Personal protective equipment (PPE)

Published online:

Table 1. Personal protective equipment in different patient settings

3.1. Management of potential exposures

4. Continuing routine patient services

Published online:

5. Patient area ventilation

6. Procedures during COVID-19

6.1. Pulmonary function testing

6.2. Bronchoscopy

6.3. Nebulization

7. Management of chronic lung diseases

7.1. Asthma

7.2. Chronic obstructive pulmonary disease

7.3. Interstitial lung diseases

8. COVID-19 care

8.1. Imaging in suspected cases

Published online:

Table 2. Imaging modalities for COVID-19

Published online:

8.2. Methods of testing

8.3. Stratification of severity, site of care and prognostication

8.4. Management of hypoxia

8.4.1. High-flow nasal cannula (HFNC)

8.4.2. Noninvasive ventilation

8.4.3. Invasive mechanical ventilation

8.4.4. Extra-corporeal membrane oxygenation (ECMO)

8.5. Specific medications

Published online:

Table 3. Guidelines for approved therapies in COVID-19

8.5.1. Steroids

8.5.2. Remdesivir

8.5.3. Anticoagulants

8.5.4. Prophylactic antibiotics

8.5.5. Antipyretics

8.5.6. Other drugs

Published online:

Table 4. Use of experimental therapies in COVID-19

8.6. Monitoring COVID-19 patients

8.7. Cardio-pulmonary resuscitation

9. Conclusion

10. Expert opinion

Disclosure statement

Article highlights

Declaration of interest

Reviewer disclosures

References

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