Does non-invasive ventilation even work in critically ill COVID-19 patients?

The last post in this blog discussed whether non-invasive ventilation (NIV) can be effective in acute respiratory failure for any cause, and examined only randomized controlled trials of the intervention. But is COVID-19 different?

There aren’t any controlled experimental trials of non-invasive ventilation for COVID-19 or related coronaviruses, so for this post we’ve had to look at retrospective observational studies. The evidence is weaker here. But it still looks like NIV can be helpful, at least in a large fraction of cases.

COVID-19: Experiences

In a retrospective analysis of 191 patients with confirmed COVID-19 in two hospitals in Wuhan, China, 41 received high-flow nasal cannula oxygen therapy; 33 (80%) of those died. 26 patients received non-invasive mechanical ventilation; 24 (92%) of those died. Finally, 32 received invasive mechanical ventilation; 31 (97%) of those died.  This was not a statistically significant difference between the survival rates of different respiratory support techniques.[1]

In a retrospective study of 60 severe COVID-19 patients from Jiangsu Province, China, 16 patients (26.7%) had respiratory failure. 14 patients received non-invasive mechanical ventilation (NIV), 15 received high-flow nasal cannula (HFNC), 6 received both NIV and HFNC, and 3 received invasive mechanical ventilation.  14 (93%) of the HFNC patients improved; 9 (64%) of the NIV patients improved; this is not a statistically significant difference. 3 patients needed invasive mechanical ventilation; the paper did not list which therapies they had previously failed.[2]

A retrospective on 631 patients in Jiangsu Province, China, reports that they were able to keep the rate of invasive mechanical ventilation under 1%, far below the Chinese average, despite a 10% rate of critically ill patients, by continuously monitoring high-risk patients and placing them on NIV or HFNC.[3]

In a retrospective of 53 critically ill COVID-19 patients from Wuhan, 33 were treated with HFNC and 52% survived; 29 were placed on NIV and 26% survived; and 22 were placed on invasive ventilation and 14% survived.  Of those placed on NIV, 48% had to be placed on invasive ventilation.[4]

In a preliminary (not-peer-reviewed) retrospective of 45 critically ill patients from Guangdong Province, China, with COVID-19, 6 (13.3%) were treated with standard oxygen therapy, 13 (28.9%) were treated with HNFC, 6 (13.3%) with NIV (all on a BiPAP), and 20 (44.4%) with invasive mechanical ventilation. Only one patient (2.2%) died in this cohort, compared to 62% in Wuhan. No patients treated with non-invasive oxygen therapies needed to be intubated.[5]

In a retrospective study of 267 confirmed COVID-19 patients from Chongqing Municipality, China, 5 patients received invasive mechanical ventilation, 35 received non-invasive ventilation, 12 received HFNC, and 91 patients received standard oxygen therapy.  4 (1.5%) patients died in the entire study. All 50 patients with severe disease received oxygen, and all 50 needed further respiratory therapy; 2/35, or 5.7%, of patients on non-invasive ventilation needed to be intubated.[6]

Conclusions Based on COVID-19 Published Data

There have been no controlled studies of non-invasive ventilation for COVID-19.

In a total of 70 COVID-19 patients, from three Chinese studies, treated with non-invasive ventilation, 23% needed to be intubated.  This is well within the range of failure of NIV for other causes of acute respiratory failure, and leaves it as an option that can still work in the majority of cases.

In a total of 90 patients treated with HFNC, 56% died; in a total of 69 patients treated with NIV, 72% died; in a total of 54 patients treated with invasive ventilation, 93% died.  There is no statistically significant difference in the death rates between groups. 

The WHO’s clinical guidelines [7] on the use of NIV and HFNC in COVID-19 are as follows:

High-flow nasal oxygen (HFNO) should only be used in selected patients with hypoxemic respiratory failure. 

Non-invasive ventilation (NIV) should only be used in selected patients with hypoxemic respiratory failure.

 Patients treated with either HFNO or NIV should be closely monitored for clinical deterioration. 

Remark 1: Adult HFNO systems can deliver 60 L/min of gas flow and FiO2 up to 1.0. Paediatric circuits generally only handle up to 25 L/min, and many children will require an adult circuit to deliver adequate flow.

Remark 2: Due to uncertainty around the potential for aerosolization, HFO, NIV, including bubble CPAP, should be used with airborne precautions until further evaluation of the safety can be completed. 

Remark 3: Compared with standard oxygen therapy, HFNO reduces the need for intubation (42). Patients with hypercapnia (exacerbation of obstructive lung disease, cardiogenic pulmonary oedema), hemodynamic instability, multiorgan failure, or abnormal mental status should generally not receive HFNO, although emerging data suggest that HFNO may be safe in patients with mild-moderate and non-worsening hypercapnia (42, 43, 44). Patients receiving HFNO should be in a monitored setting and cared for by experienced personnel capable of endotracheal intubation in case the patient acutely deteriorates or does not improve after a short trial (about 1 hour). Evidence-based guidelines on HFNO do not exist, and reports on HFNO in other coronavirus-infected patients are limited (44).

Not much is known about the use of NIV and HFNO in COVID-19.  If possible, patients being given these therapies should be monitored in case they fail and the patient needs to be urgently intubated. However, what little evidence we have is in line with the results from other severe pulmonary diseases like pneumonia: in a majority of cases, non-invasive respiratory therapy can suffice and invasive mechanical ventilation can be avoided.


Among 1512 patients with SARS in Guangdong Province, China, there were 58 deaths, for a case fatality rate of 3.8%, the lowest in the world. The author attributes this success to prompt treatment with corticosteroids and, in 20-30% of cases, with non-invasive ventilation (usually with a CPAP mask.)[8]

In a Hong Kong case series of SARS patients, non-invasive ventilation was reported to be able to avoid intubation in ⅔ of patients.[9]

In a retrospective study of two hospitals in Hong Kong, one which used non-invasive ventilation with a BiPAP and one which only used invasive ventilation for SARS, 21.4% out of 42 patients needed to be intubated at the NIV hospital compared to 41.2% out of 451 patients at the invasive-ventilation hospital, a significant (p = 0.012) reduction in the need for intubation.  Also, the mortality rate was lower (9.5% vs 25.1%, p = 0.024) in the NIV hospital. Only 8/21 (38%) of NIV-treated patients needed to be intubated. No healthcare workers acquired SARS at the NIV hospital.[10]

In a meta-analysis of 4 studies comprising 96 SARS patients treated with NIV, the non-invasive ventilation treatment failed in a total of 51 patients, or 53%.[11]

 In 17 studies of patients with H1N1 influenza comprising 551 patients treated with NIV, 338 or 61% failed the treatment.  The paper summarizes the use of NIV in H1N1 as follows: “NIV has a role in the management of early respiratory failure due to pH1N1 infection; however, in a strictly controlled environment with close monitoring of healthcare workers and with adequate precautions for prevention of infection transmission. NIV has no role in severe respiratory failure and ARDS related to severe pH1N1 infection.” [11]


In 32 critically ill healthcare workers with MERS, 13 received NIV and 26 received invasive ventilation; that is, 7/13, or 54%, of patients treated with NIV failed and needed to be intubated. [12] 


In COVID-19 and in other coronavirus epidemics (SARS and MERS), non-invasive ventilation significantly reduces the need for intubation. In the case of SARS, NIV has been shown to significantly reduce mortality as well. In these viruses, NIV has high failure rates – 20-60%, depending on the disease – so ideally it should be closely monitored in case the patient needs to be intubated. However, NIV succeeds often enough that it makes sense to use it for critically ill patients when invasive ventilation is not an option. (Some patients have a Do Not Intubate order, for instance.)  We don’t know much yet about how well it works in COVID-19, and there are no randomized studies, but from what little evidence we have, it seems that there’s a sizable proportion of patients who can benefit.


[1]Zhou, Fei, et al. “Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.” The Lancet (2020).

[2]Wu, Jian, et al. “Clinical characteristics of imported cases of COVID-19 in Jiangsu province: a multicenter descriptive study.” Clinical Infectious Diseases (2020).

[3]Sun, Qin, et al. “Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province.” Annals of Intensive Care 10.1 (2020): 1-4.

[4]Yang, Xiaobo, et al. “Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.” The Lancet Respiratory Medicine (2020).

[5]Xu, Yonghao, et al. “Clinical findings in critical ill patients infected with SARS-Cov-2 in Guangdong Province, China: a multi-center, retrospective, observational study.” medRxiv (2020).

[6]Yang, Xiaobo, et al. “Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.” The Lancet Respiratory Medicine (2020).

[7]World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020. No. WHO/2019-nCoV/clinical/2020.4. World Health Organization, 2020.

[8]Zhong, Nanshan. “Management and prevention of SARS in China.” Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 359.1447 (2004): 1115-1116.

[9]Yam, Loretta Yc, Rong Chang Chen, and Nan Shan Zhong. “SARS: ventilatory and intensive care.” Respirology 8 (2003): S31-S35.

[10]Yam, L. Y., et al. “Non-invasive versus invasive mechanical ventilation for respiratory failure in severe acute respiratory syndrome.” Chin Med J 118.17 (2005): 1413-1421.

[11]Esquinas, Antonio M., et al. “Noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review.” European Respiratory Review 23.134 (2014): 427-438.

[12]Shalhoub, Sarah, et al. “Critically ill healthcare workers with the middle east respiratory syndrome (MERS): A multicenter study.” PloS one 13.11 (2018).