The increased risk for COVID-19 pneumonia in people who smoke cigarettes or have chronic obstructive pulmonary disease (COPD) may be at least partly explained by increased levels of an enzyme that enables the virus to more easily enter their lungs, according to a research letter published today in the European Respiratory Journal.
In the same journal, a study has identified advanced age, underlying cardiovascular or cerebrovascular illnesses, low levels of CD3+CD8+ T cells (indicating damaged immune response), and high levels of cardiac troponin (indicating heart damage) as predictors of death in patients with COVID-19 pneumonia.
Other research in the same journal found that temperature, humidity, and ultraviolet (UV) radiation had no effect on the spread of the novel coronavirus in Chinese cities.
Elevated enzyme levels put smokers, those with COPD at high risk
In the first known study on this topic, Canadian researchers sought to determine whether patients who smoked or had COPD had higher levels of angiotensin-converting enzyme 2 (ACE2) in their lower respiratory tract. People older than 55 years with significant underlying illnesses such as COPD have accounted for most cases of severe COVID-19, they noted.
Previous research has shown that ACE2 on the surface of lung cells is the doorway that allows viruses into the lungs, where they cause infection.
For the present study, the team analyzed lung samples from 21 adults with COPD and 21 healthy adults. COPD was defined as a clinical diagnosis by a board-certified respiratory physician and either a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than 70% or computed tomographic evidence of emphysema.
The researchers found significantly elevated ACE2 expression levels in patients with COPD (2.52 ±0 .66 vs. 1.70 ± 0.51 in non-COPD patients; P = 7.62×10−4) and in current smokers (2.77 ± 0.91 vs. 1.78 ± 0.39 in never smokers; P = 0.024). Levels in former smokers were between that of never and current smokers (2.00 ± 1.23).
They confirmed their findings with those of two other study groups with data on another 249 nonsmokers and former and current smokers, they said. "This may in part explain the increased risk of viral respiratory tract infection in active smokers and virus-related exacerbations in those with COPD," the authors wrote.
They recommend increased coronavirus vigilance in smokers and those with COPD to prevent and rapidly diagnose the infection.
"Patients with COPD should be counselled to strictly abide by social distancing and proper hand hygiene to prevent infection," investigator Janice Leung, MD, said in a press release. "We also found that former smokers had similar levels of ACE-2 to people who had never smoked. This suggests that there has never been a better time to quit smoking to protect yourself from COVID-19."
Tobias Welte, MD, an infectious disease expert from the European Respiratory Society who was not involved in the study, said in the release that more research is needed on the topic. "What it does not tell us is whether it's possible to manipulate ACE-2 levels to improve survival in patients infected with COVID-19 or whether this would make a difference in COPD patients who contract the infection," he said.
Four predictors of death due to severe illness
In the study on predictors of death, researchers collected demographic, clinical, and lab data from 179 adults hospitalized in Wuhan Pulmonary Hospital in China with COVID-19 pneumonia from Dec 25, 2019, to Feb 7.
Ninety-seven of the patients were male, and the mean age was 57.6 years (range, 18 to 87). As of Mar 24, 158 of the patients had been released from the hospital. The remaining 21 patients had died of multiple organ failure, largely respiratory and heart failure. Seventeen of the 21 patients who died (81%) were older than 65, while none were younger than 50. Mean time from hospitalization to death was 13.7 days (range, 3 to 33).
Univariate and multivariate logistic regression analysis showed that age of 65 years or older (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.1 to 17.4; P = 0.023), underlying cardiovascular or cerebrovascular diseases (OR, 2.5; 95% CI, 0.755 to 8.044; P = 0.007), CD3+CD8+ T cells ≤ 75 cell/μL (OR, 4.0; 95% CI, 1.132 to 14.006; P < 0.001), and cardiac troponin I ≥ 0.05 ng/mL (OR, 4.1; 95% CI, 1.166 to 14.253; P < 0.001) were linked to an increased risk of death.
Low levels of CD3+CD8+ T cells may indicate that the coronavirus damages the immune response, the authors said. Cardiac troponins are proteins that indicate heart injury.
Patients who died were much older than survivors (70.2 ± 7.7 years vs. 56.0 ± 13.5 years, P < 0.001) and had more high blood pressure (61.9% vs. 28.5%, P = 0.005) and cardiovascular and cerebrovascular diseases (57.1% vs. 10.8%, P < 0.001). There was no difference in the incidence of diabetes, chronic digestive disorders, tuberculosis, chronic liver or kidney disease, peripheral vascular disease, or cancer between the two groups (all P > 0.05).
Patients who died were more likely than survivors to have shortness of breath (85.7% vs. 44.9%, P < 0.001), fatigue (61.9% vs. 36.7%, P = 0.033), sputum production (57.1% vs. 27.2%, P = 0.010), headache (23.8% vs. 7.6%, P = 0.033), and a high respiratory rate (P = 0.016).
Warmer weather won't slow spread
In the weather-related study, researchers at Fudan University in Shanghai gathered data on 17 cities inside Hubei province and 207 outside with at least 10 confirmed COVID-19 cases as of Mar 9 from the National Health Commission and the Provincial Health Commissions of China.
The underlying hypothesis was that spread of the coronavirus may diminish in summer, when higher levels of vitamin D improve immune responses, there is more UV exposure, and children are not clustered together in schools.
The investigators calculated the R0 (R-naught) for 12 cities inside Hubei and 50 outside with more than 50 cases as of Feb 10, the peak of the pandemic in China. The R0 reflects how many people each infected person will in turn infect.
Using multiple regression methods, the investigators evaluated the associations between daily mean temperature, relative humidity, and UV radiation and the spread of the virus from early January to early March in the 224 cities.
After adjusting for relative humidity and UV radiation, temperature had no significant link to cumulative incidence rate (chi-square = 5.03, P = 0.28) or R0 (chi-square = 0.93, P = 0.92) in cities inside or outside of Hubei (blue points), indicating that coronavirus transmission would not change with rising temperatures.
Neither was UV radiation significantly associated with cumulative incidence rate (chi-square = 5.50, P = 0.24) or R0 (chi-square = 0.91, P = 0.92) after adjusting for temperature and relative humidity, indicating that spread would not change with increasing UV exposure.
The authors identified no significant association between relative humanity, maximum temperature, and minimum temperature with cumulative incidence rate or R0. "In summary, our study does not support the hypothesis that high temperature and UV radiation can reduce the transmission of COVID-19," they wrote. "It might be premature to count on warmer weather to control COVID-19."