Clinical characteristics and risk factors analysis of viral shedding time in mildly symptomatic and asymptomatic patients with SARS-CoV-2 Omicron variant infection in Shanghai

Objective To analyze the clinical characteristics and risk factors of viral shedding time in mildly symptomatic and asymptomatic patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2 and BA2.2) infection in Shanghai, and the effect of traditional Chinese medicine (TCM) treatment, so as to provide a reference basis for epidemic prevention, control and clinical treatment. Methods A total of 6,134 asymptomatic or mildly symptomatic Omicron-infected patients admitted to Tianhua Road fangcang shelter hospital in Jinshan, Shanghai, between April 2022 and May 2022 were included. Demographic characteristics and clinical histories were collected and compared in subgroups according to the different durations of viral shedding. Spearman's correlation analysis was performed to explore the association between virus shedding time and clinical variables. Multiple linear regression was used to evaluate the risk factors for viral shedding time. Result Most patients with asymptomatic and mildly symptomatic Omicron infection were male, and more than half of patients had a viral shedding time of 8–15 days. The patients were divided into three groups according to the time of viral shedding: short-duration (≤ 7 days), intermediate-duration (8–15 days) and long-duration group (≥16 days). The proportion of patients aged ≤ 29 years was the highest in the short-duration group (30.2%), whereas the proportion of patients aged 50–64 yeas was the highest in the long-duration group (37.9%). The proportion of patients with the chronic non-communicable diseases among the short-, intermediate- and long-duration groups was 6.2, 9.4, and 14.9%, respectively. Among them, hypertension was the most found (4.9, 7.8, and 11.7%, respectively). By multivariate analyses, we identified that viral shedding time of Omicron variants was independently negatively correlated with male patients, TCM treatment, and manual laborers, while it was independently positively associated with age and hypertension. Additionally, TCM treatment could significantly shorten the length of viral shedding time, especially for men, age ≥30 years, comorbid chronic non-communicable diseases, unemployed people and manual worker. Conclusions Our results suggested that age and hypertension were independent risk factors for the duration of viral shedding in asymptomatic and mildly symptomatic omicron infected patients. TCM can effectively shorten viral shedding time.

Is it possible to flatten-the-curve after the initial outbreak of Covid-19? A data-driven modeling analysis for Omicron pandemic in China (preprint)

In the current coronavirus disease 2019 (COVID-19) pandemic, the Omicron variant of severe acute respiratory syndrome coronavirus 2 has become the predominant strain circulating worldwide. In China, enormous controversies exist regarding the dynamic zero tolerance (DZT) and totally no inventions (TNI) strategies for preventing the spread of the Omicron variant. Currently, China is gradually relaxing the COVID-19 measures from DZT level. In such situations, the flatten-the-curve (FTC) strategy, which decreases and maintains the low rate of infection to avoid overwhelming the healthcare system by adopting relaxed nonpharmaceutical interventions (NPIs) after the initial outbreak, has been perceived as most appropriate and effective method to prevent the spread of the Omicron variant. Hence, we established a data-driven model of Omicron transmission based on the pandemic data of Macau, Hong Kong, and Singapore in 2022 to deduce the overall prevention effect throughout China. In the current immunity level without any NPI applied, more than 12.7 billion (including asymptomatic individuals) were infected with the Omicron variant within 90 days, but the daily new infections sharply declined; moreover, Omicron outbreak would result to 1.49 million deaths within 180 days. The application of FTC could decrease the deaths by 36.91% within 360 days. Age-stratified analyses showed that the NPI application among individuals aged >60 years would also result in 0.81 million deaths within 360 days, and the application of FTC strategy through treatment with anti-COVID drugs can reduce the number of deaths to 0.40 million. In a model of completed vaccination, the application of TNI strategy would also result in 0.56 million deaths and slightly decrease the infection numbers. The strict implementation of FTC policy combined with completed vaccination and drug use, which only resulted in 0.19 million deaths in an age-stratified model, will help end the pandemic within about 240 days. The pandemic would be terminated within a shorter period of time without resulting in a high fatality rate; therefore, the FTC policy could be strictly implemented through enhancement of immunity and drug use.

Bioinformatics analysis on structure and function of the spike glycoprotein of SARS-CoV-2 and its prokaryotic expression

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV -2) is a highly pathogenic and rapidly spreading pathogen. It can invade and infect cells by recognizing receptors on the surface of host cells with spike (5) glycoprotein. Systematic bioinformatics analysis and prokaryotic expression of the S protein can aid understanding of its function and clarify the molecular mechanism of viral infection mediated by this protein. The physicochemical properties, subcellular localization, post - translational modifications and protein - interaction network of the S protein were analyzed systematically using Protparam. Pfam, TMHMM ExPASy - ProtScale, PSORT II, SignalP, UniProt, NetPhos 3.1. NetNGlyc 1.0, NetOGlyc 4.0. BLAST and other bioinformatics software and databases. In addition. Clustal X2 and MEGA7.0 were used to analyze the homology and phylogeny of S glycoproteins based on amino-acid sequences. Finally, recombinant expression vector of the S glycoprotein was constructed by molecular cloning technology and expressed in Escherichia call. Results showed that the S glycoprotein is composed of 1,273 amino acids, with a molecular weight of 141.2 kD and an isoelectric point of 6.24. It had two coiled helical structures and one transmembrane helix region. It was a hydrophobic protein, contained a spike receptor-binding domain and 52 glycoprotein domain. This protein was distributed mainly in the endoplasmic-reticulum membrane (39.1%) and cell membrane (21.7%) of host cells. and contained 136 potential phosphorylation sites and 20 possible glycosylation sites. SARS-CoV, SARS-Coy WI-120 and bat coronavirus HKU3 showed the highest sequence identity with the spike-glycoprotein sequence of SARS-CoV-2 (76%). SARS-CoV-2, SARS-CoV and bat coronavirus clustered into a large branch. suggesting that they may have a common ancestor. The S protein was expressed mainly in the precipitate after centrifugation of bacterial lysates, which lays a foundation for future structural analysis and vaccine development. The S glycoprotein was highly conserved between SARS-CoV and bat coronavirus, suggesting that this glycoprotein has a vital role in viral invasion into host cells. SARS-CoV-2 may have a common ancestor with SARS-CoV and bat coronavirus. Our study provides an important data basis for expression. purification. structural and functional analysis of the S glycoprotein of SARS-CoV-2. Our data may help to reveal the biological functions of the S glycoprotein, and provide a scientific basis for the design and screening of new antiviral drugs targeting this protein.

The Occurrence of Heavy Air Pollution during the COVID-19 Outbreak in Beijing, China: Roles of Emission Reduction, Meteorological Conditions, and Regional Transport

To prevent the spread of coronavirus disease (COVID-19) and mitigate the epidemic risk, strict lockdown measures were implemented in Beijing during the quarantine period, significantly reducing human activities. However, severe air pollution episodes occurred frequently in Beijing. To explore the occurrence of severe air pollution during the quarantine period, the impacts of emission reductions, meteorological conditions, and regional transport on heavy air pollution were individually evaluated using the Community Multiscale Air Quality (CMAQ) model. Observations showed that the more unfavorable meteorological conditions which occurred during the pandemic as compared to the corresponding 2019 levels, including higher temperature, relative humidity, and frequency of strong southerly winds, and lower HPBL, led to an increase in PM2.5 concentrations. The model results also showed that the meteorological conditions in February 2020 favored PM2.5 formation. The PM2.5 concentrations were mainly dominated by regional transport, which became more significant in the quarantine period than in 2019, suggesting the importance of joint control on regional sources for reducing heavy air pollution. This study highlights that, although the emissions in Beijing and surrounding regions were largely reduced during the quarantine period, severe air pollution in Beijing did not reduce due to the unfavorable meteorological conditions.

Patients with COVID-19 and HBV Coinfection are at Risk of Poor Prognosis (preprint)

Objective: Aim to study: 1. Whether there is a difference in the risk of death / critical illness between different stages of HBV (Resolved hepatitis B, HBeAg (-) CHB/infection, HBeAg (+) CHB/infection and HBV reactivation) coinfected with COVID-19; 2.If there is a difference, whether it is due to abnormal liver function and how much.Methods: This cohort study included all covid-19 inpatients of a single-center tertiary care academic hospital in Wuhan, Hubei, China, between February 4, 2020 and followed up to April 14, 2020. A total of 2899 COVID-19 patients were included as participants in this study and they were divided into five groups based on infection status of hepatitis B. Follow-up for mortality and ICU was carried out during hospitalization.Results: The median follow-up time was 39 (IQR,30-50) days with 66 deaths and 126 ICU. after adjustment, compared to patients without CHB, the hazard ratio (HR) for ICU was 8.02 (95% CI: 4.77-13.49) for patients with HBeAg (+) CHB/infection, and 5.15 (95% CI: 1.66-16.02) for those with HBV reactivation. And HR for death was 11.57 (95% CI: 6.30-21.26) for patients with HBeAg (+) CHB/infection. The results of mediating effect indicated the total effect of HBeAg (+) CHB/infection on death/ICU is partially mediated by abnormal liver function, accounted for 79.60% and 73.53%, respectively.Conclusion: COVID-19 patients coinfected with HBV at HBeAg (+) CHB/infection stage will increase the risk of poor prognosis, and abnormal liver function partially mediates the increased risk effect of poor prognosis caused by the coinfection.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital.

Innenrücktitelbild: Aptamer Blocking Strategy Inhibits SARS‐CoV‐2 Virus Infection

Eine Aptamer‐Blockierungsstrategie zur Hemmung der SARS‐CoV‐2‐Infektion wird von Honglin Chen, Yanling Song, Chaoyong Yang et al. im Forschungsartikel auf S. 10354 demonstriert. Eine Aptamer‐Sonde wurde so konstruiert, dass sie an das Spike‐Protein von SARS‐CoV‐2 bindet, was die Infektion des Virus hemmt, indem es die Interaktion des Virus mit ACE2‐Rezeptoren auf der Zellmembran blockiert.

Aptamer Blocking Strategy Inhibits SARS‐CoV‐2 Virus Infection

The COVID‐19 pandemic caused by SARS‐CoV‐2 is threating global health. Inhibiting interaction of the receptor‐binding domain of SARS‐CoV‐2 S protein (SRBD) and human ACE2 receptor is a promising treatment strategy. However, SARS‐CoV‐2 neutralizing antibodies are compromised by their risk of antibody‐dependent enhancement (ADE) and unfavorably large size for intranasal delivery. To avoid these limitations, we demonstrated an aptamer blocking strategy by engineering aptamers’ binding to the region on SRBD that directly mediates ACE2 receptor engagement, leading to block SARS‐CoV‐2 infection. With aptamer selection against SRBD and molecular docking, aptamer CoV2‐6 was identified and applied to prevent, compete with, and substitute ACE2 from binding to SRBD. CoV2‐6 was further shortened and engineered as a circular bivalent aptamer CoV2‐6C3 (cb‐CoV2‐6C3) to improve the stability, affinity, and inhibition efficacy. cb‐CoV2‐6C3 is stable in serum for more than 12 h and can be stored at room temperature for more than 14 days. Furthermore, cb‐CoV2‐6C3 binds to SRBD with high affinity (Kd=0.13 nM) and blocks authentic SARS‐CoV‐2 virus with an IC50 of 0.42 nM.

Aptamer Blocking Strategy Inhibits SARS-CoV-2 Virus Infection

Eine Aptamer-Blockierungsstrategie zur Hemmung der SARS-CoV-2-Infektion wird von Honglin Chen, Yanling Song, Chaoyong Yang et?al. in ihrem Forschungsartikel demonstriert (DOI: 10.1002/ange.202100225). Eine Aptamer-Sonde wurde so konstruiert, dass sie an das Spike-Protein von SARS-CoV-2 bindet, was die Infektion des Virus hemmt, indem es die Interaktion des Virus mit ACE2-Rezeptoren auf der Zellmembran blockiert.

Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic SARS-CoV-2 carriers and symptomatic/presymptomatic COVID-19 patients (preprint)

Summary Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. We enrolled 193 subjects infected with SARS-CoV-2 in Ningbo and Zhoushan, Zhejiang, China from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of immunoglobulin M (IgM) and IgG against SARS-CoV-2. Of those, 31 were asymptomatic carriers, 149 were symptomatic patients, and 14 were presymptomatic patients. Compared to symptomatic patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower levels of C-reactive protein and viral load, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients ( P =0.030). The proportion of those persistently seropositive for IgG was higher in COVID-19 patients than in asymptomatic carriers ( P =0.037). Viral load was higher in symptomatic than presymptomatic patients. Viral shedding was longer in presymptomatic patients than in asymptomatic carriers. Conclusively, asymptomatic carriers have a higher antiviral immunity to clear SARS-CoV-2 than do symptomatic patients and this antiviral immunity is not contributable to humoral immunity.

Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic SARS-CoV-2 carriers and symptomatic/ presymptomatic COVID-19 patients (preprint)

Background Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial.Methods A total of 193 subjects in Ningbo and Zhoushan, Zhejiang, China, were enrolled in this study from January 21 to March 6, 2020. All subjects were tested positive for SARS-CoV-2 genomic RNA by quantitative reverse transcription PCR and then followed up to monitor the dynamics of serum antibody immunoglobulin M (IgM) and immunoglobulin G (IgG) against SARS-CoV-2 using enzyme-linked immunosorbent assays. Scatter diagram to demonstrate the distribution of IgM and IgG among asymptomatic carriers and COVID-19 patients were generated by R.Results Of the 193 subjects, 31 were asymptomatic SARS-CoV-2 carriers, 149 were symptomatic COVID-19 patients, and 14 were COVID-19 patients during the incubation. Compared to symptomatic COVID-19 patients, asymptomatic SARS-CoV-2 carriers were younger and had higher levels of white blood cell and lymphocyte, lower levels of C-reactive protein (CRP) and viral load, and shorter viral shedding time. Seroconversion of IgM against SARS-CoV-2 from positive to negative in asymptomatic carriers took 7.50 (IQR, 4.75–11.50) days, which was significantly shorter than 25.50 (IQR, 6.75–56.75) days in COVID-19 patients (P = 0.030). The proportion of those persistently seropositive for IgG against SARS-CoV-2 was higher in COVID-19 patients than in asymptomatic carriers (66.1% vs. 33.3%, P = 0.037). Viral load was higher in symptomatic than presymptomatic COVID-19 patients. Viral shedding was longer in presymptomatic COVID-19 patients than in asymptomatic carriers. In 4 familial clusters of SARS-CoV-2 infection, asymptomatic carriers were mainly children and young adults while severe COVID-19 was mainly found in family members older than 60 years with underlying diseases. Asymptomatic carriers acquired infection more from intra-familial transmission than did COVID-19 patients (89% vs. 61%, P = 0.028).Conclusion Asymptomatic carriers might have a higher antiviral immunity to clear SARS-CoV-2 than symptomatic COVID-19 patients and this antiviral immunity might not be contributable to humoral immunity. The severity of COVID-19 is associated with older age and underlying diseases in familial clustering cases.

BTB and CNC homology 1 inhibition ameliorates fibrosis and inflammation via blocking ERK pathway in pulmonary fibrosis.

OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) are still suffering from unfavorable survival. BTB and CNC homology1 (Bach1) is a regulator of oxidative stress and participates in the pathogenesis of multiple lung diseases. Thus, this study aimed to determine the effect of Bach1 knockdown on fibrosis and inflammation in pulmonary fibrosis (PF) mice and cell models. METHODS: Bleomycin induced PF mice were constructed and treated with Bach1 siRNA adenovirus (BLM + Bach1 siRNA group), control siRNA adenovirus (BLM + Control siRNA group) or normal saline (BLM group), then lung tissues were collected for Bach1 expression detection, H&E staining and Masson's trichrome staining. Afterwards, collagen type I alpha 1 chain (COL1A1) and interleukin-6 (IL-6) expressions in serum and bronchoalveolar lavage fluid (BALF) were examined. Subsequently, mouse lung fibroblasts (MLFs) were collected from PF mice and treated with TGF-ß1 to construct PF cell model, which was treated with Bach1 siRNA adenovirus (TGF-ß1 + Bach1 siRNA group) and MAP kinase (ERK) inhibitor U0126 alone (TGF-ß1 + U0126 group) or in combination (TGF-ß1 + U0126 + Bach1 siRNA group), then alpha-smooth muscle actin (α-SMA), fibronectin 1 (Fn1), COL1A1, IL-6 expressions and cell viability were detected. RESULTS: Lung tissue Bach1 mRNA and protein expressions were upregulated in PF mice compared to control mice. Bach1 knockdown reduced lung fibrosis (displayed by Masson's trichrome staining) and inflammation (displayed by H&E staining), then downregulated serum and BALF expressions of COL1A1 and IL-6 in PF mice. Subsequently, in PF cell model, Bach1 knockdown blocked ERK pathway, but did not affect Smads, c-Jun N-terminal kinase (JNK) or thymoma viral proto-oncogene 1 (Akt) pathways. Further experiments revealed that Bach1 knockdown repressed cell viability, α-SMA, Fn1, IL-6 and COL1A1 expressions in PF cell model, then ERK inhibition by U0126 enhanced these effects. CONCLUSIONS: Bach1 is involved in the PF pathogenesis via modulating ERK signaling pathway.

Media Exposure to COVID-19 Information, Risk Perception, Social and Geographical Proximity, and Self-Rated Anxiety in China (preprint)

Background: The coronavirus disease 2019 (COVID-19) is an emerging infectious disease that spreads around the world. The lack of effective antiviral drugs and vaccines, along with the relatively high mortality rate and high contagiousness, has raised strong public concerns over COVID-19, especially for people living in the most severely affected areas. This study aimed to clarify the influencing factors for the anxiety level among the Chinese people during the COVID-19 pandemic, with a particular focus on the media exposure to different COVID-19 information.MethodsA total of 4991 respondents were randomly recruited from a national online panel from February 12 th , 2020 to February 14 th , 2020, a period when the number of COVID-19 cases surpassed 10,000 in a single day, with the total cases in China reaching up to 90000. The relationships between media exposure of COVID-19 information, social and geographical proximity to COVID-19, risk perceptions were assessed using hierarchical ordinary least squares regression analysis. Results: The media exposure to COVID-19 information was differently associated with anxiety. Meanwhile, the anxiety level was found to be high in respondents who personally knew someone infected with COVID-19 or those who living in an area with reported cases. Respondents who perceived more risks also reported a higher level of anxiety. Conclusions: This study highlights the role of media exposure in affecting individuals’ anxiety level during the COVID-19 pandemic. Besides, it is recommended that government and health professionals are recommended to adopt effective risk communication strategies to protect citizens’ mental health during the pandemic.

Presymptomatic Transmission and Diverse Progression of Familial Clustering Covid-19 Cases in Zhoushan, China (preprint)

Background Novel coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused emerging infectious disease, firstly identified in Wuhan (Hubei, China), is pandemic. However, data concerning presymptomatic SARS-CoV-2 transmission and disease diversity among family members are limited. Herein, We investigated the epidemiological and clinical characteristics of presymptomatic transmission-caused familial clustering cases of SARS-CoV-2 infection in Zhoushan island, China.Methods All family members were tested for SARS-CoV-2 genomic RNA by quantitative reverse transcription PCR in 3 different samples and serum antibody immunoglobin M (IgM) and IgG against SARS-CoV-2. Exposure identification, laboratory test, and imaging were performed according to the national guideline of COVID-19 (7th edition, China).Results Of the 6 cases, index case who ever met his relative with COVID-19 from Xianning, Hubei on January 26–31, 2020, transmitted SARS-CoV-2 to his family members in Zhoushan via visiting family during January 31 and February 3, 2020. The index was identified as common-type COVID-19 on February 6, 2020. All 5 family members were infected with SARS-CoV-2. Of those, a 7-year-old girl was an asymptomatic carrier whereas her grandparents, especially her grandfather, were very sick. Case 6 (grandfather) remained positive for SARS-CoV-2 RNA in his sputum specimen in subsequent 2 months. Case 2 (mother) tested negative for SARS-CoV-2 RNA in all samples but positive for IgM and IgG to SARS-CoV-2 since February 9, 2020.Conclusions Presymptomatic transmission of SARS-CoV-2 causes familial cluster of COVID-19. Exposed to the same source of infection, family members present their differences in disease severity and viral clearance.

Presymptomatic transmission and diverse progression of familial clustering COVID-19 cases in Zhoushan, China (preprint)

Background Novel coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused emerging infectious disease, firstly identified in Wuhan (Hubei, China), is pandemic. However, data concerning presymptomatic SARS-CoV-2 transmission and disease diversity among family members are limited.Objectives To investigate the epidemiological and clinical characteristics of presymptomatic transmission-caused familial clustering cases of SARS-CoV-2 infection in Zhoushan island, China.Methods All family members were tested for SARS-CoV-2 genomic RNA by quantitative reverse transcription PCR in 3 different samples and serum antibody immunoglobin M (IgM) and IgG against SARS-CoV-2. Exposure identification, laboratory test, and imaging were performed according to the national guideline of COVID-19 (7th edition, China).Results Of the 6 cases, index case who ever met his relative with COVID-19 from Xianning, Hubei on January 26–31, 2020, transmitted SARS-CoV-2 to his family members in Zhoushan via visiting family during January 31 and February 3, 2020. The index was identified as common-type COVID-19 on February 6, 2020. All 5 family members were infected with SARS-CoV-2. Of those, a 7-year-old girl was an asymptomatic carrier whereas her grandparents, especially her grandfather, were very sick. Case 6 (grandfather) remained positive for SARS-CoV-2 RNA in his sputum specimen in subsequent 2 months. Case 2 (mother) tested negative for SARS-CoV-2 RNA in all samples but positive for IgM and IgG to SARS-CoV-2 since February 9, 2020.Conclusions Presymptomatic transmission of SARS-CoV-2 causes familial cluster of COVID-19. Exposed to the same source of infection, family members present their differences in disease severity and viral clearance.

Extended SIR prediction of the epidemics trend of COVID-19 in Italy and compared with Hunan, China (preprint)

Background: Coronavirus Disease 2019 (COVID19) is currently a global public health threat. Outside of China, Italy is one of the most suffering countries with the COVID19 epidemic. It is important to predict the epidemics trend of COVID19 epidemic in Italy to help develop public health strategies. Methods: We used time series data of COVID 19 from Jan 22,2020 to Mar 16,2020. An infectious disease dynamic extended susceptible infected removed (eSIR) model, which covers the effects of different intervention measures in dissimilar periods, was applied to estimate the epidemic trend in Italy. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credible interval (CI). Hunan, with similar total number of populations in Italy, was used as a comparative item. Results: In the eSIR model, we estimated that the basic reproductive number for COVID 19 was respectively 4.10 (95% CI: 2.15 to 6.77) in Italy and 3.15(95% CI: 1.71 to 5.21) in Hunan. There would be totally 30 086 infected cases (95%CI:7920-81 869) under the current country blockade and the endpoint would be Apr 25 (95%CI: Mar 30 to Aug 07) in Italy. If the country blockade is imposed 5 day later, the total number of infected cases would expand the infection scale 1.50 times. Conclusion: Italy's current strict measures can efficaciously prevent the further spread of COVID19 and should be maintained. Necessary strict public health measures be implemented as soon as possible in other European countries with a high number of COVID19 cases. The most effective strategy needs to be confirmed in further studies.