Letter to the Editor: Obesity hypoventilation syndrome and severe COVID-19
Authors: Jiao-Feng Huang, Xiao-Bo Wang, Kenneth I. Zheng, Wen-Yue Liu, Jun-Jie Chen, Jacob George, Ming-Hua Zheng
Journal: Metabolism (2020)

Dear Sir, The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a pandemic by the World Health Organization [[1]World Health Organization WHO characterizes COVID-19 as a pandemic.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happenDate: March 11, 2020Google Scholar]. Obesity is a common cause to aggravate the severity of respiratory diseases [[2]Gao F. Zheng K.I. Wang X.B. et al.Obesity is a risk factor for greater COVID-19 severity.Diabetes Care. 2020; Crossref Scopus (284) Google Scholar] which may place obese patients infected by SARS-CoV-2 at risk for pulmonary complications. We here report the case of a 23-year-old man who attended Wenzhou Central Hospital, Wenzhou, China (on January 21, 2020) after five days of fever, chills, headache, nasal congestion, cough and mild dyspnoea. Other medical comorbidities included metabolic associated fatty liver disease (MAFLD) [[3]Eslam M. Newsome P.N. Anstee Q.M et al.A new definition for metabolic associated fatty liver disease: an international expert consensus statement.J. Hepatol. 2020; https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (2084) Google Scholar] for five years, obstructive sleep apnoea hypopnea syndrome (OSAHS) for two years, and gout for one year, the latter treated with oral benzbromarone and bicarbonate. At the time of hospital admission, the most relevant clinical findings at baseline included a body mass index (BMI) of 37.3 kg/m2 and body temperature of 39.4 °C, white blood cell (WBC) count of 4.8 × 109/L, neutrophil count of 3.1 × 109/L, lymphocyte count of 1.2 × 109/L, platelet count of 217 × 109/L, C-reactive protein (CRP) of 37.8 mg/L, fasting blood glucose of 4.9 mmol/L, total cholesterol of 4.38 mmol/L, high-density lipoprotein of 0.62 mmol/L, low-density lipoprotein of 1.62 mmol/L, lactic acid dehydrogenase of 271 U/L, uric acid of 602 μmol/L, ferritin of 796 μg/L, lactate of 2.2 mmol/L, and PaO2/FiO2 of 205 mm Hg. His chest computed tomography (CT) scan showed bilateral ground-glass opacities (Fig. 1A ). On the suspicion of COVID-19, the attending physician ordered salivary testing which was positive for SARS-CoV-2 by real-time RT-PCR assay (RT-PCR). The patient was immediately transferred to the isolation ward and commenced on nebulized α-interferon (5,000,000 IU) twice per day, oral lopinavir/ritonavir (200 mg/50 mg) twice per day, and oral arbidol (200 mg) thrice per day as recommended by the Chinese COVID-19 Interim Management Guidance (3rd edition) [[4]China National Health Commission Diagnosis and treatment of COVID-19 in China.3rd edition. January 22, 2020http://wwwnhcgovcn/yzygj/s7653p/202001/f492c9153ea9437bb587ce2ffcbee1fashtmlDate accessed: January 22, 2020Google Scholar]. Because of the increased serum CRP, the patient was suspected to have a bacterial co-infection and empirical treatment with intravenous amoxicillin sodium and clavulanate potassium (1.2 g) thrice per day was commenced. Given his worsening dyspnoea and continued PaO2/FiO2 of <300 mm Hg, the patient was subsequently given continuous high-flow oxygen inhalation (6 L/min) via a nasal catheter. Of note, the dyspnoea improved with arterial PaO2 fluctuating between 94·5–127.5 mm Hg, while the arterial PaCO2 remained high (46.8–53.9 mm Hg). Several attempts over the next 72 h to improve the PaCO2 levels by lowering the oxygen therapy flow rate were to no avail. On day nine, the patient had significant improvement in symptoms with PaCO2 < 40 mm Hg. A follow-up chest CT scan showed marked improvement in pulmonary infiltration (Fig. 1B). Subsequently, a follow-up CT of the chest on day twenty-one showed evidence of further improvement (Fig. 1C) and he was discharged after two negative oropharyngeal swab tests and one faecal nuclei acid test for the virus by RT-PCR. On follow-up two weeks after discharge, his chest CT showed resolution of the pulmonary infiltrates (Fig. 1D). This patient was diagnosed with type II acute respiratory failure as the likely result of COVID-19 in the context of other comorbidities including obesity and MAFLD. This is an interesting case in that up to now, only type I acute respiratory failure has been reported in severe COVID-19 patients [[5]Guan W.J. Ni Z.Y. Hu Y. et al.Clinical Characteristics of Coronavirus Disease 2019 in China.N. Engl. J. Med. 2020; https://doi.org/10.1056/NEJMoa2002032Crossref Scopus (20078) Google Scholar]. Our patient's PaCO2 levels remained elevated despite multiple attempts to adjust his oxygenation therapy. Fortunately, his hypercapnia improved on day nine which we believe was due to the improvement in pulmonary infiltrates. Previous studies have shown that obesity may cause restrictive lung disease with reduced vital capacity [[6]Marik P.E. Desai H.D. Characteristics of patients with the "malignant obesity hypoventilation syndrome" admitted to an ICU.J. Intensive Care Med. 2013; 28: 124-130Crossref PubMed Scopus (95) Google Scholar]. In our patient, obese hypoventilation syndrome (i.e. BMI ≥ 30 kg/m2 and PaCO2 > 45 mm Hg) was observed, possibly the result of combined severe pulmonary viral and bacterial infection; this can progress to malignant hypoventilation syndrome, a condition typically characterized by a poor prognosis [[6]Marik P.E. Desai H.D. Characteristics of patients with the "malignant obesity hypoventilation syndrome" admitted to an ICU.J. Intensive Care Med. 2013; 28: 124-130Crossref PubMed Scopus (95) Google Scholar]. The current practice guidance for treatment of COVID-19 suggests non-invasive oxygenation management targeting dyspnoeic individuals with PaO2/FiO2 levels below 300 mm Hg or primarily in those with type I acute respiratory failure. However, no strategies exist for managing COVID-19 patients with obesity, chronic obstructive pulmonary disease or other diseases that may cause type II acute respiratory failure. In this patient, worsening hypercapnia might have led to serious sequelae if he had not recovered from his illness. Potential management strategies in deteriorating patients include the use of different oxygenation therapies. In high-flow oxygenation therapy, a moisturized and temperature-controlled airflow provides appropriate respiratory support with moderate positive airway pressure and helps remove mucus plugs to facilitate better oxygen exchange in the lungs and, thereby, increasing PaO2/FiO2. However, its effect on improving simultaneous hypercapnia is uncertain. Alternatively, non-invasive ventilation with an oxygen mask might significantly improve both hypoxemia and hypercapnia, in addition to managing the OSAHS. However, non-invasive ventilation is often uncomfortable and is associated with non-compliance and increases the risk of mucus plug accumulation in the lungs. Invasive ventilation may be the most effective strategy for these patient in that all the abovementioned complications can be appropriately managed, especially when the arterial blood gas pH is <7.3 (or correspondingly increased PaCO2 levels). However, the risk that needs to be balanced is of nosocomial infection through prolonged intubation and transmission risk to healthcare providers of SARS-CoV-2. Overall, in obese patients combined with SARS-CoV-2 infection, especially in slow to recover patients, early invasive ventilation therapy might be a more appropriate strategy for managing a rapidly deteriorating pulmonary function. That said, it is reasonable to speculate that obesity with coexisting COVID-19 may predispose patients to the risk of more severe conditions such as obese hypoventilation syndrome. This is more likely in those that are older and with multiple comorbid diseases such as MAFLD, dyslipidaemia and OSAHS, and therefore less likely to be have adequate compensatory organ capacity. Future studies are needed to confirm these observations and to better understand the underlying mechanisms linking SARS-CoV-2 infection with the occurrence of type II acute respiratory failure in obese patients. The authors have no conflicts of interest related to this article.