A group of physicians in Wuhan, China, who are treating patients with the 2019 novel coronavirus have gone the extra mile to share their clinical experiences with colleagues around the world.
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Nanshan Chen, MD, of Jinyintan Hospital, Wuhan, and his team conducted a retrospective study on 99 cases and, in very short order, published their initial findings in the Lancet online on Jan. 29. These findings could guide action in other cases and help clinicians all over the world create treatment plans for patients of the 2019-nCoV.
The findings show that and characteristics of those with fatal infections align with the MuLBSTA score – an early warning model for predicting viral pneumonia–related mortality, according to a case review.
Of 99 patients who presented with 2019-nCoV pneumonia at Jinyintan Hospital between Jan. 1 and Jan. 20, 67 were men, the mean age was 55.5 years, and 50 patients had chronic diseases.
“All the data of included cases have been shared with [the World Health Organization]. The study was approved by Jinyintan Hospital Ethics Committee and written informed consent was obtained from patients involved before enrollment when data were collected retrospectively,” the researchers noted.
Nearly half of the patients (49%) lived or worked near a specific seafood market, suggesting disease clustering.
Clinical manifestations affecting the majority of patients included fever and cough in 83% and 82% of patients, respectively. Other symptoms included shortness of breath in 31%, muscle aches in 11%, confusion in 9%, headache in 8%, sore throat in 5%, and rhinorrhea, chest pain, diarrhea, and nausea and vomiting in 1%-4% of patients, the investigators found.
Imaging showed bilateral pneumonia in 75% of cases, multiple mottling and ground-glass opacity in 14%, and pneumothorax in 1%. Organ function damage was present in a third of patients at admission: 17% had acute respiratory distress syndrome (ARDS) – including 11 patients who worsened quickly and died of multiple organ failure. Eight percent had acute respiratory injury, 3% had acute renal injury, 4% had septic shock, and 1% had ventilator-associated pneumonia, they said, noting that all cases were confirmed by real-time polymerase chain reaction.
A notable laboratory finding was reduced absolute lymphocyte counts in most patients, the investigators said.
All patients were treated in isolation and 76% received antiviral treatment with oseltamivir, ganciclovir, lopinavir, or ritonavir for 3-14 days (median, 3 days). Most patients also received antibiotic treatment, including a single antibiotic in 25% of cases and combination therapy in 45%, with most antibiotics used to cover “common pathogens and some atypical pathogens,” they said, adding that “when secondary bacterial infection occurred, medication was administered according to the results of bacterial culture and drug sensitivity.”
Cephalosporins, quinolones, carbapenems, tigecycline against methicillin-resistant Staphylococcus aureus, linezolid, and antifungal drugs were used, and duration ranged from 3 to 17 days (median, 5 days).
Nineteen patients also received steroid treatments.
As of Jan. 25, 31 patients had been discharged and 57 remained hospitalized. Of the 11 who died, the first 2 were a 61-year-old man and a 69-year-old man, each diagnosed with severe pneumonia and ARDS. The first experienced sudden cardiac arrest and died on admission day 11, and the second died of severe pneumonia, septic shock, and respiratory failure on admission day 9. Neither had underlying disease, but both had a long history of smoking, the investigators noted.
“The deaths of these two patients were consistent with the MuLBSTA score,” they wrote, explaining that the scoring system takes into account multilobular infiltration, lymphopenia, bacterial coinfection, smoking history, hypertension, and age.
Eight of the nine other patients who died had lymphopenia, seven had bilateral pneumonia, five were over age 60 years, three had hypertension, and one was a heavy smoker, they added.
Most coronavirus infections cause mild symptoms and have good prognosis, but some patients with the 2019-nCoV, which was identified Jan. 7 following the development of several cases of pneumonia of unknown etiology in Wuhan, develop fatal disease. The paucity of data regarding epidemiology and clinical features of pneumonia associated with 2019-nCoV prompted the current retrospective study at the center where the first cases were admitted, the investigators explained.
They noted that the sequence of 2019-nCoV “is relatively different from the six other coronavirus subtypes, including the highly pathogenic severe acute respiratory syndrome (SARS)-CoV and Middle East Respiratory Syndrome (MERS)-CoV, as well as the human coronaviruses (HCoV)-OC43, -229E, -NL63, and -HKU1 that induce mild upper respiratory disease, but can be classified as a betacoronavirus with evidence of human-to-human transmission.
Mortality associated with SARS-CoV and MERS-CoV have been reported as more than 10% and more than 35%, respectively; at data cutoff for the current study, mortality among the 99 included cases was 11%, which is similar to that in another recent 2019-nCoV report, they said.
The finding of greater risk among older men also has been seen with SARS-CoV and MERS-CoV, and the high rate among individuals with chronic diseases, mainly cerebrovascular disease, cardiovascular disease, and diabetes, also has been reported with MERS-CoV, they added.
“Our results suggest that 2019-nCoV is more likely to infect older adult males with chronic comorbidities as a result of the weaker immune functions of these patients,” they wrote.
Coinfection with bacteria and fungi occurred in some patients, particularly those with severe illness, and cultures most often showed A. baumannii, K. pneumoniae, A. flavus, C. glabrata, and C. albicans, and the findings of reduced absolute lymphocyte values in most patients suggests that “2019-nCoV might mainly act on lymphocytes, especially T lymphocytes, as does SARS-CoV,” they noted.
Given the rapid progression with ARDS and septic shock in some patients in this review, “early identification and timely treatment of critical cases is of crucial importance,” they said.
“Use of intravenous immunoglobulin is recommended to enhance the ability of anti-infection for severely ill patients, and steroids (methylprednisolone 1-2 mg/kg per day) are recommended for patients with ARDS, for as short a duration of treatment as possible,” they added.
Further, since some studies suggest that a substantial decrease in lymphocyte count indicates consumption of many immune cells by coronavirus, thereby inhibiting cellular immune function, damage to T lymphocytes might be “an important factor leading to exacerbations of patients,” they wrote, adding that “[t]he low absolute value of lymphocytes could be used as a reference index in the diagnosis of new coronavirus infections in the clinic.”
The MuLBSTA score also should be investigated to determine its applicability for predicting mortality risk in patients with 2019-nCoV infection, they added.
The current study is limited by its small sample size; additional studies are needed to include “as many patients as possible in Wuhan, in other cities in China, and even in other countries to get a more comprehensive understanding of 2019-nCoV,” they said.
The National Key R&D Program of China funded the study. The authors reported having no conflicts of interest.
SOURCE: Chen N et al. Lancet. 2020 Jan 29. doi: 10.1016/S0140-6736(20)30211-7.