Adjusted control rate closely associated with the epidemiologic evolution of the recent COVID-19 wave in Shanghai, with 94.3% of all new cases being asymptomatic on first diagnosis

Summary Background The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available. Methods A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced. Results Since January 23, 2020, we enrolled a cluster of eight youngsters with COVID-19 (median age [range], 22 [16–23] years; six males) originating from Patient-Index returning from Wuhan to Hefei on January 19. Patient-Index visited his 16-year-old female cousin in the evening on his return, and met 15 previous classmates in a get-together on January 21. He reported being totally asymptomatic and were described by all his contacts as healthy on January 19-21. His very first symptoms were itchy eyes and fever developed at noon and in the afternoon on January 22, respectively. Seven youngsters (his cousin and six classmates) became infected with COVID-19 after a-few-hour-contact with Patient-Index. None of the patients and contacts had visited Wuhan (except Patient-Index), or had any exposure to wet-markets, wild-animals, or medical-institutes within three months. For affected youngsters, the median incubation-period was 2 days (range, 1–4). The median serial-interval was 1 day (range, 0–4). Half or more of the eight COVID-19-infected youngsters had fever, cough, sputum production, nasal congestion, and fatigue on admission. All patients had mild conditions. Six patients developed pneumonia (all mild; one bilateral) on admission. As of February 20, four patients were discharged. Conclusions SARS-CoV-2-infection presented strong infectivity during the incubation-period with rapid transmission in this cluster of youngsters outside Wuhan. COVID-19 developed in these youngsters had fast onset and various nonspecific atypical manifestations, and were much milder than in older patients as previously reported.

In late February, 2022, a wave of SARS-CoV-2 infection rapidly appeared in Shanghai, China. According to the Shanghai Municipal Health Commission, as of May 4, 2022, 601 942 cases have been identified, including 547 056 asymptomatic carriers. 503 people have died with or from COVID-19. Phylogenetic features of SARS-CoV-2 viral genomes from 129 patients in this period, and inferring their relationship with those available on the GISAID database, indicated that all of the new viral genomes in Shanghai were clustered into the SARS-CoV-2 BA.2.2 sub-lineage. Of note, BA.2 is a sub-lineage of the omicron variant of SARS-CoV-2 (B.1.1.159). Multiple sub-lineages of BA.2 have been characterised, many of which appear to show distinct regional distribution patterns. At present, BA2.2 only represents a small sub-lineage of BA.2 worldwide (1993 [0·25%] of 800 366 seqences in GISAID), sequences of which have been detected in Hong Kong (839 [42·10%]), the UK (742 [37·20%]), and Australia (121 [6·10%]). We assessed the potential risk of various feature mutations on BA2.2 on the severity of COVID-19 and found that these mutations showed no significance in their distributions between severe to critical and mild to moderate COVID-19, suggesting that the observed disease severity is probably mainly attributed to comorbidities. Although omicron BA.2 evolves towards less virulent, a higher rate of severe outcomes and considerable mortality have been reported in unvaccinated people, especially older adults. 1 This has been confirmed in Hong Kong, where health authorities have reported 9115 deaths among 1 192 765 people with SARS-CoV-2 (crude case fatality rate 0·76%) during the fifth wave of the pandemic, as of May 4, 2022. 2 The crude case fatality rate in those older than 60 years (19·30% of this age group has not been vaccinated) was 2·70%. Comparatively, only 2% of New Zealand's population older than 60 years has not been vaccinated, which is highly correlated with a low COVID-19 crude case fatality rate of 0·07%. In Shanghai, with a population of 25 million, the overall vaccination coverage now exceeds 90%; however, vaccination coverage has remained low in older adults—62% of 5·8 million people older than 60 years have been vaccinated, and only 38% have received a booster vaccination. As of May 4, 2022, among the 503 people who died with or from COVID-19, only 25 patients had received at least one dose of COVID-19 vaccine. The vaccination rate for the deceased patients was only 4·97%. If no strict public health measures were taken, such as large scale viral nucleic acid and antigen screening, quarantine of infected cases and close contacts in shelter hospitals and hotels, respectively, and lockdown of districts with severe outbreak, the number of severe to critical cases and the resultant death toll could be high among the older people without vaccination. The strict and comprehensive pandemic control strategies in Shanghai are therefore actually to reduce the number of people infected and to provide early diagnosis and appropriate treatment for severe COVID-19 so that the case fatality rate can be minimised, and to buy time for full vaccination coverage. Local citizens have suffered in their daily lives from inconveniences of lockdown. Some people even developed mental health symptoms as a reaction to the unexpected crisis. Facing these challenges, social workers and many volunteers have made great contributions to the care of the people in need from both material and psychological perspectives. The food and daily consumable supply are ensured thanks to the support of many other cities and provinces. Through the unprecedented efforts of health professionals in Shanghai and those coming from other cities, and of people from all the circles in Shanghai, the strategies have shown very promising results, as indicated by an R0 of 9·5 at the beginning of the wave to an Rt of 0·67 on May 1, 2022. 3 The number of newly infected cases, after peaking at 27 719 on April 13, 2022, has now dropped to 4651 cases, as of May 4, 2022. Life-saving efforts are continuing with the improvement of public health measures and social services on one hand, and treatment of hundreds of severe to critical cases on the other. Meanwhile, the return to normal life and work is proceeding in a stepwise manner, and people in Shanghai is hailing the light at the end of the tunnel. Shanghai's great efforts against omicron are essential for China to exit from the pandemic in a larger sense. As a leading economic centre and an open city in China, Shanghai has huge exchanges with other cities and regions in the country, so the spill-out of virus to other places, especially in the central and western regions with insufficient medical resources and lower vaccination coverage, could have unimaginably severe consequences. In this regard, strict control strategies in Shanghai might have prevented the continuous spread and a large number of deaths. According to the Chinese National Health Commission, 4 about 49 million people older than 60 years have not yet been vaccinated, and among this population, a considerable number suffer from underlying diseases. The persistence of dynamic zero COVID-19 community transmission in Shanghai and other cities will overcome weak links in the immunological barrier in populations across the country. Fortunately, besides the available vaccines and heterologous vaccination approach, several new vaccines specifically targeting omicron variants, including mRNA vaccine, inactivated vaccine, and recombinant Spike protein subunit vaccine, have also been approved for clinical trials in China and could soon be available for emergency use. The next challenge will be to enhance the communication between the health-care providers and the public to overcome the vaccine hesitancy and make the vaccination service accessible to all people, the older and vulnerable people in particular. Moreover, the production of effective anti-SARS-CoV-2 drugs and preparation of sufficient medical resources, including intensive care units and teams for severe diseases and training of grassroots-level health-care workers capable of last-mile services of disease control and prevention are on the way. We believe that China will win the fight against the COVID-19 pandemic in joint efforts with other members of the international community in the not too distant future. For New Zealand's COVID-19 data and statistics see https://www.health.govt.nz/covid-19-novel-coronavirus/covid-19-data-and-statistics For the Shanghai Municipal Health Commission's SARS-CoV-2 data see https://wsjkw.sh.gov.cn/

Letter to the Editor We read with interest the letter by Dimeglio et al reporting the impact of vaccination and pre-immunity on the proliferation of Omicron BA.1 and BA.2 sublineages in France [1]. The new emerging Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading worldwide. The Omicron strain has multiple spike protein mutations compared with other variants of concern, such as the Alpha and Delta strains [2]. Consequently, there is concern that serum antibody activity against the Omicron strain in vaccinated or convalescent persons will be weaker than that against previous SARS-CoV-2 strains [3, 4]. Because the characteristics of infectivity and treatment response differ among Omicron sublineages [5, 6], it is important to understand the evolutionary process in real time. To determine the viral lineage of SARS-CoV-2, we performed whole genome sequencing analyses or TaqMan assays using SARS-CoV-2-positive samples (n = 1,297) collected consecutively in Yamanashi, Japan from September 2021 to March 2022 (Supplemental materials) [7, 8, 9]. During this period, we identified Delta strain (n = 159) and Omicron strain (n = 1,139). After the first case of Omicron was identified in January 2022, Omicron rapidly replaced Delta as the prevalent strain of SARS-CoV-2 (Figure 1 A). Figure 1 Changes in Omicron strain prevalence SARS-CoV-2 strains identified from September 2021 to March 2022. Orange boxes indicate Delta strains, and blue boxes indicate Omicron strains. (B, C) Sublineage of Omicron strains detected from January 2022 to March 2022, indicated by BA.1 (pink), BA.1.1 (green), and BA.2 (blue). The number of samples detected per day (B) and the frequency of detection (C) are shown. Figure 1 The whole genome sequencing data were analyzed using PANGOLIN (version 3.1.20), and BA.1 (n = 5), BA.1.1 (n = 992), and BA.2 (n = 142) were identified as sublineages of Omicron (Figure 1B). Sublineage BA.1.1 was the dominant sublineage of Omicron from January to mid-February 2022; however, the incidence of sublineage BA.2 increased from mid-February 2022 onward, with this sublineage becoming dominant by the end of March (Figure 1B and 1C). The average frequency for the seven-day period from March 8 to March 14 was 62.2% (51/82) for sublineage BA.1.1 and 37.8% (31/82) for sublineage BA.2, whereas from March 15 to March 21 it was 29.3% (27/92) for sublineage BA.1.1 and 70.7% (65/92) for sublineage BA.2. These results indicate an extremely rapid replacement of sublineage BA.1.1 by sublineage BA.2 and a higher transmissibility of sublineage BA.2 compared with sublineage BA.1.1. To investigate the underlying factors for the high transmissibility of Omicron sublineage BA.2, we performed an RT-qPCR analysis of the viral load in the nasopharyngeal swabs collected from patients infected with sublineage BA.1.1 (n = 748) or sublineage BA.2 (n = 118). The median viral load (log10 copies/mL) was 5.7 (range: 0.2–7.9) for sublineage BA.1.1 versus 6.4 (range: 0.3–8.2) for sublineage BA.2 (Figure 2 A). The median Ct value for sublineage BA.1.1 was 19 (range: 11–38) versus 17 (range: 10–38) for sublineage BA.2 (Figure 2B). There are significant differences in the viral load between cases of sublineage BA.1.1 and sublineage BA.2 (Figure 2A, p = 4.8 × 10−4, Student's t-test) and Ct value (Figure 2B, p = 1.6 × 10−3, Student's t-test). However, the median age of infected patients was not significantly different between these sublineages (35 years [range: 0–101 years] for BA.1.1 vs. 34.5 years [range: 0–90 years] for BA.2; p = 0.1, Student's t-test) (Figure 2C). These results indicate that the viral load in nasopharyngeal swabs is higher for sublineage BA.2 than for sublineage BA.1.1 and that sublineage BA.2 is more contagious. Figure 2 Viral load and age of infected patients for sublineages BA.1. and BA.2. (A, B) The viral load and Ct values in Omicron sublineages BA.1.1 (n = 748) and BA.2 (n = 118) were analyzed by RT-qPCR. Box plots show the viral load (A) and Ct values (B) in BA.1.1 and BA.2. (C) Box plot shows the age of patients infected with sublineage BA.1.1 or BA.2. (D, E) Relationship between patient age and viral load (D) or Ct value (E). Pearson's correlation coefficient (r) is noted in the figures. The gray background of the regression line indicates the 95% confidence interval. Figure 2 We next examined whether the viral load varied with patient age. There was no apparent correlation between patient age and viral load or Ct value for either sublineage BA.1.1 or BA.2 (Figure 3D and 3E). The Pearson's correlation coefficients for sublineage BA.1.1 were r = −0.0075 (p = 0.84) for patient age and viral load and r = 0.0070 (p = 0.85) for patient age and Ct value, and those for sublineage BA.2 were r = −0.032 (p = 0.73) for patient age and viral load and r = 0.034 (p = 0.71) for patient age and Ct value (Figures 2D and 2E). These results indicate that the viral load remained fairly high in Omicron-infected patients regardless of their age. In summary, this study indicates that after the expansion of the SARS-CoV-2 Delta strain, a rapid spread of the Omicron strain occurred. Sublineage BA.1 was very minor in Japan when Omicron was first discovered. First, sublineage BA.1.1 expanded dominantly and was then gradually replaced by sublineage BA.2. A transition from sublineage BA.1.1 to sublineage BA.2 was clearly observed over approximately one month. The results of the present study show that the amount of viral load in the nasopharyngeal swab was higher for sublineage BA.2 than for sublineage BA.1.1. These epidemiological and viral characteristic results indicate that Omicron sublineage BA.2 is more transmissible than sublineage BA.1.1. Although a high incidence of household COVID-19 infections stemming from young children has been reported [10], our results indicate that the Omicron strain retains a fairly high viral load across age groups, which may contribute to the high infectivity of the Omicron strain and its accelerated spread. These data provide insights for determining appropriate COVID-19 prevention and control measures for homes, schools, workplaces, and facilities for the elderly during the spread of Omicron strain viruses. Declaration of Competing Interest None