Most Read Articles
Jairia Dela Cruz, 22 Apr 2020
A wristwatch-like device that monitors pulse, breathing and blood oxygen levels of the user allows physicians to provide care remotely both in hospital and nontraditional settings, and may help in the fight against the coronavirus disease 2019 (COVID-19) pandemic.
Roshini Claire Anthony, 27 May 2020

The use of a vaginal cleansing intervention prior to Caesarean delivery reduced the incidence of surgical site infections (SSIs), according to a study presented at ACOG 2020. However, the addition of intravenous (IV) azithromycin prophylaxis had no added impact on SSI rates. 

Pank Jit Sin, 21 May 2020

Persons suffering from asthma should pay particular attention to SARS-CoV-2 precautionary measures such as social distancing, regular handwashing, and wearing of masks on top of keeping their asthma in control. This is because data collected so far paints a bleaker picture for asthmatics than the normal population should they catch COVID-19.

Natalia Reoutova, Yesterday

A comprehensive review of neurological disorders reported during the current coronavirus disease 2019 (COVID-19) pandemic demonstrates that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the central nervous system (CNS), the peripheral nervous system (PNS) and muscles, leading the Environmental Neurology Specialty Group of the World Federation of Neurology to propose implementation of international neurological registries.

SARS-CoV-2 triggers suboptimal innate immune responses despite efficient replication

Christina Lau
16 Apr 2020
From left: Dr Hin Chu, Prof Kwok-Yung Yuen, Dr Jasper Chan

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers much weaker innate immune responses than the 2003 SARS-CoV despite more efficient replication, according to a study conducted in ex vivo lung tissues donated by patients in Hong Kong.

The lung tissues, donated by six patients (mean age, 53 years; 50 percent male) who underwent wedge resection or lobectomy for lung tumour at the Queen Mary Hospital, were challenged in parallel by SARS-CoV-2 and SARS-CoV (as control). According to investigators from the University of Hong Kong (HKU), this ex vivo lung model provides a unique opportunity for side-by-side comparison of virological and host response characteristics that cannot be achieved with clinical studies in patients or with animal models. [Clin Infect Dis 2020, doi: 10.1093/cid/ciaa410]

“Our results showed that despite more efficient replication in human lungs, SARS-CoV-2 activated less expression of interferons [IFNs] and inflammatory mediators than SARS-CoV,” said Dr Hin Chu of the Department of Microbiology, HKU.

SARS-CoV-2-N antigen was consistently detected in higher abundance and in broader areas of lung tissues of all donors, with a 2.30-fold to 2.87-fold higher relative fluorescence intensity (p<0.0001 to 0.041), compared with SARS-CoV-N antigen.

“Within a 48-hour period, SARS-CoV-2 produced 3.20-fold more infectious virus particles than SARS-CoV in the human lung tissues [p<0.024], as shown in area-under-the-curve analysis,” said Chu.

Both viruses could infect type I and II pneumocytes as well as alveolar macrophages. However, the degree of innate immune activation was much lower with SARS-CoV-2.

While SARS-CoV infection resulted in significant upregulation of type I (IFNβ), II (IFNγ) and III (IFNλ1, IFNλ2 and IFNλ3) IFNs in the human lung tissues, SARS-CoV-2 infection did not significantly trigger the expression of any IFN at all evaluated time points.

Furthermore, SARS-CoV infection resulted in significant activation of 11 of 13 (84.62 percent) representative proinflammatory cytokines/chemokines. In contrast, SARS-CoV-2 infection led to upregulation of only five (38.46 percent) of these key inflammatory mediators.

“Our findings may explain the high viral load in respiratory secretions of patients with coronavirus disease 2019 [COVID-19] who have mild or no symptoms, as well as the high transmissibility of SARS-CoV-2,” said Dr Jasper Chan of the Department of Microbiology, HKU.

“These findings also suggest that using IFNβ as the backbone of cocktail therapy, together with antiviral therapy, is viable and reasonable in the treatment of COVID-19,” said Professor Kwok-Yung Yuen of the Department of Microbiology, HKU.

However, as viral load peaks in respiratory specimens of COVID-19 patients at the time of symptom onset, the investigators cautioned that antiviral therapy may not be very effective if given later than 48 hours after the onset of symptoms.

“High-dose corticosteroids and antagonists against major inflammatory mediators, such as interleukin-6, should only be used together with effective antiviral therapies to avoid oversuppression of innate immune response in COVID-19 patients, as SARS-CoV-2 is already suppressing the host innate immune response at the beginning of infection,” they added.

A limitation of the study is that short-lasting ex vivo human lung tissue explant culture cannot represent the effect of host systemic inflammatory response and adaptive immune response. Furthermore, the characteristics of different SARS-CoV-2 strains could not be studied in the ex vivo model due to the limited supply of human lung tissues.

Nevertheless, the findings highlight the importance of universal masking, in addition to hand washing and social distancing, as a key measure to control the spread of COVID-19 in the community, the investigators emphasized.

Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Infectious Diseases - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
Jairia Dela Cruz, 22 Apr 2020
A wristwatch-like device that monitors pulse, breathing and blood oxygen levels of the user allows physicians to provide care remotely both in hospital and nontraditional settings, and may help in the fight against the coronavirus disease 2019 (COVID-19) pandemic.
Roshini Claire Anthony, 27 May 2020

The use of a vaginal cleansing intervention prior to Caesarean delivery reduced the incidence of surgical site infections (SSIs), according to a study presented at ACOG 2020. However, the addition of intravenous (IV) azithromycin prophylaxis had no added impact on SSI rates. 

Pank Jit Sin, 21 May 2020

Persons suffering from asthma should pay particular attention to SARS-CoV-2 precautionary measures such as social distancing, regular handwashing, and wearing of masks on top of keeping their asthma in control. This is because data collected so far paints a bleaker picture for asthmatics than the normal population should they catch COVID-19.

Natalia Reoutova, Yesterday

A comprehensive review of neurological disorders reported during the current coronavirus disease 2019 (COVID-19) pandemic demonstrates that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the central nervous system (CNS), the peripheral nervous system (PNS) and muscles, leading the Environmental Neurology Specialty Group of the World Federation of Neurology to propose implementation of international neurological registries.