Coronavirus disease 2019 (COVID-19) update for critical care physicians

Beginning from December 8, 2019, several cases of pneumonia of unknown origin were reported from Wuhan, the capital of the Chinese province of Hubei. The initial cluster of cases was traced to the Huanan live animal and seafood market. The causative pathogen has hence been identified as an enveloped RNA beta coronavirus with genealogical similarity to the SARS coronavirus and named SARS-CoV-2. Initial reports from Wuhan pointed towards an atypical pneumonia and was termed coronavirus disease 2019 (COVID-2019). At the time of writing, COVID-19 has afflicted 107,691 patients across 98 countries and has caused 3,661 deaths. Thirty-nine cases have been reported in India so far, from Delhi (NCR), Uttar Pradesh, Telangana, Rajasthan, and Kerala (1). 

Mode of transmission

The primary mode of COVID-19 transmission is through respiratory droplets generated when an infected person coughs, sneezes, or talks. Droplets that settle on the eyes, nose, or mouth of a person in close proximity leads to the transmission of infection. Transmission can also occur by touching the face with contaminated hands. Respiratory droplets do not remain suspended in the air for long; hence, a distance of six feet away from an infected person may be considered safe (2). Coronaviruses may contaminate metal, glass, or plastic surfaces that may remain infective for several days. Contact with such contaminated surfaces (fomites) and subsequent transfer to the face by touch may also be an important mode of transmission. 

Airborne transmission, distinct from droplet infection, is characterized by viruses that drift through the air. It is unclear if airborne transmission occurs with COVID-19 infection. The possibility of airborne transmission requires the use of additional protective measures, including N95 masks.   

R0, pronounced R-naught, is the basic reproduction number and indicates the transmissibility of a disease when special quarantining or isolation measures are not undertaken. In simple terms, R0 indicates the number of people to whom an afflicted person can transmit the infection. From preliminary analysis, the R0 for COVID-19 has been estimated to be between 2.2 and 3.6 (3). The capability to transmit infection can be highly variable between individuals. There are some infected individuals who are capable of transmitting the disease to a much larger number of people than most others (high R0). Such individuals with a high potential for transmission are called “super-spreaders”. 

Patient screening and triage

Patients who present with fever and respiratory symptoms with an epidemiological link to COVID-19 should carry a high index of suspicion for the disease. The epidemiological link may involve (a) travel to an area that experienced an outbreak, (b) close contact with an individual with confirmed or high risk of infection, or (c) close contact with an individual with respiratory symptoms who had been in a geographic location that witnessed an outbreak within a 14-day period prior to the onset of symptoms. Fever may not be a presenting symptom in all cases. Patients who present with bilateral pneumonia with the risk factors mentioned above carry a high index of suspicion even in the absence of fever. As the geographic area of involvement is expanding, clinicians need to keep themselves updated on the list of affected countries and territories. Following several generations of spread with a country, local transmission of disease occurs, and patients may present with no history of travel to a location with a known outbreak.

Critically ill patients may present to the emergency department from the community or by inter-hospital transfer to the intensive care unit. In such instances, a detailed enquiry should be carried out to ensure appropriate screening and infection control precautions should be followed. 

Infection control measures 

Environmental

Although the predominant mode of transmission of COVID-19 disease appears to be through droplet and contact with respiratory secretions, airborne transmission may occur, and appropriate precautions are recommended in high-risk situations, especially when treating patients who are critically ill. The use of high-flow nasal oxygen, nebulizers, non-invasive ventilation, bag-mask ventilation, the performance of laryngoscopy and endotracheal intubation are likely to generate aerosols, that may predispose to transmission of the virus. 

Considering the uncertainty regarding airborne transmission, isolation rooms with negative pressure and frequent air exchanges are advisable for suspected cases. If sufficient airborne isolation areas are unavailable, patients should be accommodated in single rooms behind closed doors. Anterooms to enable caregivers to put on (don) and remove (doff) personal protective equipment (PPE) should also be available. 

Personal protective equipment

Healthcare workers who care for critically ill patients with suspected or confirmed COVID-19 disease must use PPE. Operating room scrubs or full coveralls should form the first layer of protection beneath PPE. The PPE must include fluid-resistant gowns and gloves, goggles with side protection, hair covers or hoods, and fit-tested N95 respirator masks. Caregivers should also wear disposable shoe covers or water-resistant shoes that can be decontaminated. Doffing of PPE should be carried out carefully, with diligent hand hygiene after removal. A powered air-purifying respirator (PAPR) is often recommended and may offer greater protection compared to N95 masks. It consists of a respirator worn as a hood; it draws in and filters potentially contaminated ambient air, and delivers clean, decontaminated air to the user through the hood. 

High flow nasal oxygen, non-invasive ventilation, and nebulizer use 

Droplet and aerosol spread may occur during therapeutic interventions among patients with COVID-19 disease. When administering oxygen through nasal prongs, the patient’s face may be covered with a surgical mask to prevent droplet spread. The use of a high-flow nasal cannula may lead to aerosol generation; hence, it should be used only in locations that provide airborne isolation. Nebulized medications are best avoided due to the possibility of aerosol generation; metered-dose inhalers may be used as an alternative. Although a few patients in hypoxemic respiratory failure may be managed with NIV, extensive disease transmission may occur over a wide area, as noted during the severe acute respiratory syndrome (SARS) epidemic (4). Besides, NIV use may delay intubation leading to patient deterioration and inadequate donning of PPE during emergent intubation.  As a general rule, high-flow nasal cannulae and NIV should be used sparingly, and never outside a suitable location with droplet and airborne isolation.  

The experience so far

Several retrospective observational studies have been reported from China since the outbreak of COVID-19 disease from late December 2019. These studies offer insight regarding the presenting symptoms, clinical and radiological features, progression, and outcomes of patients with COVID-19 disease. 

Chen et al. retrospectively evaluated 99 patients with COVID-19 admitted to the Jin Yin-tan Hospital in Wuhan, the epicenter of the novel coronavirus outbreak, between January 1 to January 20, 2020. The diagnosis of COVID-19 disease was confirmed by real-time RT-PCR, and evaluation of epidemiological, demographic, clinical, and radiological features, and laboratory data were performed. Patients were followed up until Jan 25, 2020. The mean patient age was 55·5 years (SD 13·1) with a male predominance (67%). Fever and cough were the most common symptoms, followed by breathing difficulty. Chest radiography and CT imaging revealed bilateral pneumonia in 75% of patients; unilateral pneumonic infiltrates were seen in others. Extensive mottling and ground-glass opacities were the predominant features on imaging. Acute respiratory distress syndrome (ARDS) occurred in 17% of patients, acute kidney injury in 3%, and septic shock in 4% of patients. The majority of patients required supplemental oxygen therapy (75%). NIV was applied in 13%, and invasive mechanical ventilation was carried out in 4% of patients. Continuous renal replacement therapy was performed in 9%, and extracorporeal membrane oxygenation (ECMO) in 3% of patients. Eleven patients (11%) had died at the time of follow up on January 25, 2020, all from ARDS and multiorgan failure (5). 

Guan et al. retrospectively analyzed the medical records of 1099 patients (outpatients and inpatients) with laboratory-confirmed COVID-19 from 552 hospitals in China between December 11, 2019, and January 29, 2020. The diagnosis was confirmed by RT-PCR assay of nasal and pharyngeal swabs. The primary composite endpoint of admission to ICU, mechanical ventilation, or death occurred in 67 patients (6.1%). Among the components of the primary outcome, 5% of patients required ICU admission, and 2.3% required invasive mechanical ventilation, with an overall mortality of 1.4%. Among all the patients, the cumulative risk of the composite endpoint was 3.6%; among those with severe disease, the cumulative risk was 20.6%. Invasive mechanical ventilation was required in 14% of patients with severe disease; NIV was required in 32.4% of patients with severe disease. ECMO was carried out in 5 patients. The median hospital length of stay was 12 (10–14) days (6).  

Forty-one hospitalized patients were evaluated in a retrospective study of patients with confirmed COVID-19 infection at the Jin Yin-tan Hospital in Wuhan, China. Data were collected between December 16, 2019, to January 2, 2020. The median age of patients was 49 years, with male preponderance (73%). Thirty-two percent of patients had underlying co-morbidities. Fever was the most common symptom at disease onset, followed by cough, myalgia, and fatigue. Fifty-five percent of patients developed dyspnea; all patients had evidence of pneumonia on CT imaging. Lymphopenia was another common finding (63%). Twelve patients (29%) developed ARDS, five (12%) showed signs of acute cardiac injury, and five (12%) patients developed secondary infections.  Four patients (10%) required ICU admission. Six patients (15%) had died by the time of last follow up on January 2, 2020 (7). 

Yang et al. evaluated 52 critically ill patients among 710 patients with COVID-19 pneumonia admitted to the ICU of Jin Yin-tan hospital in Wuhan between late December, 2019, and January, 2020. They compared data between survivors and non-survivors. The mean age of patients was 59·7 (SD 13·3) with male predominance (67%). Thirty-two (61.5%) patients had died by day 28; the median time interval between ICU admission and death was 7 (3–11) days. Non-survivors were older, had a higher incidence of ARDS, and received NIV or invasive ventilation more often than survivors. Organ dysfunction was common, including ARDS (67%), acute kidney injury (23%), hepatic dysfunction (29%), and acute myocardial dysfunction (23%) (8). 

The Chinese Center for Disease Control and Prevention has published the largest case series of COVID-19 disease in mainland China until February 11, 2020, including 72,314 patients. Among these patients, 44, 672 (62%) were confirmed COVID-19 disease by viral nucleic acid test on throat swab samples. Most patients were aged between 30–79 years (87%). Mild disease with no pneumonia or mild pneumonia was observed in the majority of patients (81%). Severe disease occurred in 14% of patients; 5% of patients were critically ill with respiratory failure, septic shock, and multiorgan dysfunction. Among the 44, 672 confirmed cases, 1023 patients died (case fatality rate: 2.3%). The case fatality rate among patients 70–79 years was much higher (8%); no deaths were reported among children aged less than 9 years. Critically ill patients had a high case fatality rate of 49%. Patients with underlying co-morbidities had a higher mortality. Among the confirmed cases, 1716 were healthcare workers (3.8%); 14.8% developed severe disease, and five had died until February 11, 2020. 

Summary

Beginning late 2019, a novel coronavirus led to the global outbreak of an acute respiratory illness, currently designated as COVID-19 disease. Rapid spread has occurred across several geographical locations within the first few weeks. Typical initial symptoms include fever, cough, and breathlessness. A large number of patients develop pneumonic infiltrates. The disease appears to mainly affect adults between the age of 30–79 years, with a male preponderance. The large majority of patients appear to develop mild disease, and the overall mortality appears to be low (2–3%). However, a high mortality of up to 49% has been observed among critically ill patients who develop multiorgan failure. 

Healthcare workers are at high risk of acquiring the infection; appropriate infection control measures are crucial in reducing disease transmission. Screening, triage, and isolation of patients are important among those with confirmed disease and at high risk of infection. Treatment is mainly supportive;  home management and isolation may be a viable option in patients with mild disease. 

References

1.         Coronavirus Update (Live): 107,490 Cases and 3,652 Deaths from COVID-19 Wuhan China Virus Outbreak – Worldometer [Internet]. [cited 2020 Mar 8]. Available from: https://www.worldometers.info/coronavirus/

2.         Del Rio C, Malani PN. COVID-19-New Insights on a Rapidly Changing Epidemic. JAMA. 2020 Feb 28; 

3.         Zhao S, Lin Q, Ran J, Musa SS, Yang G, Wang W, et al. Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. 2020 Jan 30;92:214–7. 

4.         Li Y, Huang X, Yu ITS, Wong TW, Qian H. Role of air distribution in SARS transmission during the largest nosocomial outbreak in Hong Kong. Indoor Air. 2005 Apr;15(2):83–95. 

5.         Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020 Feb;395(10223):507–13. 

6.         Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Feb 28;NEJMoa2002032. 

7.         Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Feb;395(10223):497–506. 

8.         Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 Feb;S2213260020300795.