Nonpharmaceutical intervention is an effective measure to block respiratory virus coinfections with SARS-CoV-2

Pengcheng Liu reported that influenza virus activity dropped sharply among children in Shanghai, China, during the COVID-19 pandemic. According to their research, the infection was close to zero in the early stage of the COVID-19 pandemic. At present, the COVID-19 epidemic in China has entered the postpandemic period. Consequently, the Chinese government has announced 10 measures to optimize COVID prevention and control work since 7^th December. There is public concern that SARS-CoV-2 will circulate with other respiratory viruses and increase the probability of coinfections. Therefore, we further explored influenza virus coinfections with SARS-CoV-2 during 7^th November 2022 and ^31st December 2022 before and after the new policy.

COVID-19 poses a great challenge to China's medical and health system, either since the battle of Wuhan and Hubei in 2019 or the battle against Delta and Omicron to date.^, China has a large population. In response to the outbreak, in the past three years, China has organized and mobilized massive human and material resources and adopted strict epidemic prevention measures, such as checking health codes when entering public places, landing inspections for migrants between provinces, checking travel codes, etc. Moreover, standardized good hygiene habits are required in daily life, such as wearing masks in public and washing hands frequently, which have been demonstrated to be very effective in delaying SARS-CoV-2 transmission and remarkably decreasing the incidence and death rate worldwide. However, these anti-epidemic measures have had a great impact on the social economy and daily life. On December 7th, 2022, the Chinese National Health Commission announced ten prevention and control measures to further optimize the COVID-19 response. These new measures include scrapping negative nucleic acid results and health code requirements for entering nonspecial public places and domestic cross-regional travel, changing landing inspection into self-home quarantine in particular asymptomatic carriers and mild COVID-19 patients. The new Ten optimization measures are based on the Omicron variant with weakening “pathogenicity”, the popularization of vaccination, and the accumulation of COVID-19 prevention and control experience and have again taken an important step toward precision and science.

To extrapolate the influence of the adjustment, we counted the children who visited the Children's Hospital of Zhejiang University outpatient and inpatient departments (from November 7, 2022 to December 31, 2022) before and after the introduction of the new ten optimization measures. According to the survey, since December 7th, 2022, the number of positive patients with COVID-19 has continued to rise, and on December 22nd, the number of positive patients reached 887, with a positive rate of 68%. After a small peak of infection, the number of infected patients showed a rapid downward trend. This phenomenon is because since December 21, 2022, patients in medical institutions no longer require nucleic acid testing as a mandatory requirement. In line with this policy, the number of people taking part in the test has dropped significantly, and the corresponding number of positive patients has also decreased, but the positive rate has remained above 40%, indicating that the actual number of infected people is still increasing (Fig. 1A, Fig. 2A).

Although the severe disease rate and mortality rate are not as high as the original strain, it still places great pressure on medical institutions. To make matters worse, in the season of high incidence of respiratory viruses such as influenza, respiratory virus coinfections with COVID are more likely to occur. In the past three years, wearing masks and other epidemic prevention measures have rapidly decreased the infection rate of common respiratory viruses such as influenza, but these measures have also reduced people's immunity to those respiratory pathogens. The liberalization of epidemic prevention and control measures may cause a pandemic of these respiratory viruses, which increases the risk of combined common respiratory virus infections, such as influenza in COVID-19. Coinfection is usually considered to lead to more severe symptoms and worsen the clinical outcome of patients with COVID-19. A study from the State Key Laboratory of Virology, Wuhan University found that in COVID-19 receptor human ACE2 transgenic mice, coinfection with influenza and COVID-19 can cause more serious pathological damage to the lung and a higher COVID-19 load, which also means that it may lead to more serious secondary diseases. They found that the expression of ACE2 was slightly upregulated (2∼3 times) by influenza alone but strongly upregulated (approximately 20 times) by influenza coinfection with COVID-19. We inferred from the article that influenza virus infection can increase coronavirus infection by initiating the expression of ACE2 and accelerating the subsequent expression process. At the same time, the study also shows that^, viral infection may worsen the clinical outcome and significantly increase the probability of acute kidney injury, acute heart failure, secondary bacterial infection, multileaf infiltration and ICU admission.

In fact, according to our data, there are few people with coinfection. We selected five kinds of respiratory influenza viruses for research during this period, including Mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus and respiratory syncytial virus, which appeared as seasonal epidemics in our hospital in previous years (Fig. 1). However, according to our data, after the rapid increase in SARS-CoV-2 infection, coinfection of SARS-CoV-2 with these viruses is very rare, only 0.23% (Fig. 2). The most important reason should be that although the country has lifted restrictions on the movement of people, the public's awareness of wearing masks has become stronger. Our previous research shows that nonpharmaceutical interventions such as wearing masks and washing hands can be useful to limit the infection of common respiratory viruses, which is an effective measure to block respiratory virus infection in COVID-19.^,

In summary, nonpharmaceutical intervention is an effective measure to block SARS-CoV-2 coinfections with common respiratory virus infections.