Rapid evaluation of neutralizing antibodies in COVID-19 patients (preprint)

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for a method to rapidly and conveniently evaluate neutralizing antibody (NAb) activity in patients. Here, an up-conversion phosphor technology-based point-of-care testing (UPT-POCT) and a microneutralization assay were employed to detect total antibodies against the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and NAb activity in COVID-19 patients' sera, respectively, in order to determine if UPT-POCT could be used as a surrogate method for rapid evaluation of serum NAb activity in COVID-19 patients. In total, 519 serum samples from 213 recovered and 99 polymerase chain reaction re-positive (RP) COVID-19 patients were used in this report. We found that UPT-POCT reporting values correlated highly with NAb titers from 1:4 to 1:1024, with a correlation coefficient r = 0.9654 (P < 0.001), as well as protection rate against RP (r = 0.9886, P < 0.0001). As a significant point for reducing re-positive rate, UPT-POCT values of 4.380, corresponding to NAb titer of 1:64, may be appropriate as an indicator for evaluating high efficiency of protection. This study demonstrates that the quantitative lateral flow based UPT-POCT, could be used to rapidly evaluate NAb titer, which is of importance for assessing vaccine immunization efficacy, herd immunity, and screening patient plasma for high NAbs.

A global assessment of the impact of school closure in reducing COVID-19 spread (preprint)

Prolonged school closure has been adopted worldwide to control COVID-19. Such preemptive implementation was predicated on the premise that school children are a core group for COVID-19 transmission. Using surveillance data from the Chinese cities of Shenzhen and Anqing, we inferred that children aged 18 or below are only around half as susceptible to COVID-19 infection as adults. Using transmission models parameterized with synthetic contact matrices for 152 jurisdictions around the world, we showed that the lower susceptibility of school children substantially limited the effectiveness of school closure in reducing COVID-19 transmissibility. Our results, together with recent findings that clinical severity of COVID-19 in children is lower, suggest that school closure may not be ideal as a sustained, primary intervention for controlling COVID-19. 

Viral RNA level, serum antibody responses, and transmission risk in discharged COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study (preprint)

SummaryO_ST_ABSBackgroundC_ST_ABSManaging discharged COVID-19 (DC) patients with recurrent positive (RP) SARS-CoV-2 RNA test results is challenging. We aimed to comprehensively characterize the viral RNA level and serum antibody responses in RP-DC patients and evaluate their viral transmission risk. MethodsA population-based observational cohort study was performed on 479 DC patients discharged from February 1 to May 5, 2020 in Shenzhen, China. We conducted RT-qPCR, antibody assays, neutralisation assays, virus isolation, whole genome sequencing (WGS), and epidemiological investigation of close contacts. FindingsOf 479 DC patients, the 93 (19%) RP individuals, including 36 with multiple RP results, were characterised by young age (median age: 34 years, 95% confidence interval [CI]: 29-38 years). The median discharge-to-RP length was 8 days (95% CI: 7-14 days; maximum: 90 days). After readmission, RP-DC patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in RP-DC patients ranged from 1{middle dot}9-5{middle dot}7 log10 copies/mL (median: 3{middle dot}2, 95% CI: 3{middle dot}1-3{middle dot}5). At RP detection, the IgM, IgG, IgA, total antibody, and neutralising antibody (NAb) seropositivity rates in RP-DC patients were 38% (18/48), 98% (47/48), 63% (30/48), 100% (48/48), and 91% (39/43), respectively. Regarding antibody levels, there was no significant difference between RP-DC and non-RP-DC patients. The antibody level remained constant in RP-DC patients pre- and post-RP detection. Virus isolation of nine representative specimens returned negative results. WGS of six specimens yielded only genomic fragments. No clinical symptoms were exhibited by 96 close contacts of 23 RP-DC patients; their viral RNA (96/96) and antibody (20/20) test results were negative. After full recovery, 60% of patients (n=162, 78 no longer RP RP-DC and 84 non-RP-DC) had NAb titres of [≥]1:32. InterpretationRP may occur in DC patients following intermittent and non-stable excretion of low viral RNA levels. RP-DC patients pose a low risk of transmitting SARS-CoV-2. An NAb titre of [≥] 1:32 may provide a reference indicator for evaluating humoral responses in COVID-19 vaccine clinical trials. FundingSanming Project of Medicine in Shenzhen, China National Science and Technology Major Projects Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province of China, and Shenzhen Committee of Scientific and Technical Innovation grants.

Household transmission of COVID-19, Shenzhen, January-February 2020 (preprint)

Coronavirus disease 2019 has led to more than three million cases globally. Since the first family cluster of COVID-19 cases identified in Shenzhen in early January, most of the local transmission occurred within household contacts. Identifying the factors associated with household transmission is of great importance to guide preventive measures.

Evolving Epidemiology and Effect of Non-pharmaceutical Interventions on the Epidemic of Coronavirus Disease 2019 in Shenzhen, China (preprint)

Previous studies have demonstrated the characteristics of patients with 2019 novel coronavirus disease (COVID-19). However, the effect of non-pharmaceutical interventions on the epidemic in Shenzhen, China remains unknown. Individual data of 417 cases were extracted from the epidemiological investigations and the National Infectious Disease Information System between January 1, 2020 and February 29, 2020. On the basis of important interventions, the epidemic was divided into four periods (January 1-15, January 16-22, January 23-February 5 and after February 6). We used a susceptible-exposed-infectious-asymptomatic-recovered model to evaluate the effect of interventions. Results suggested that about 53.7% were imported from Wuhan. The median age was 47 years and 52.8% were women. Severity risk increased with age and associated with male and co-existing disorders. The attack rate peaked in the third period and drastically decreased afterwards across sex, age groups and geographic regions. Children younger than 5 years showed a higher attack rate than those aged of 6~19. The effective reproductive number decreased from 1.44 to 0.05 after the highest level emergency response since January 23. Overall, the non-pharmaceutical interventions have effectively mitigated the COVID-19 outbreak in Shenzhen, China. These findings may facilitate the introduction of public health policies in other countries and regions.

Epidemiological and clinical characteristics of COVID-19 in Shenzhen, the largest migrant city of China (preprint)

We conducted a retrospective study among 417 confirmed COVID-19 cases from Jan 1 to Feb 28, 2020 in Shenzhen, the largest migrant city of China, to identify the epidemiological and clinical features in settings of high population mobility. We estimated the median incubation time to be 5.0 days. 342 (82.0%) cases were imported, 161 (38.6%) cases were identified by surveillance, and 247 (59.2%) cases were reported from cluster events. The main symptoms on admission were fever and dry cough. Most patients (91.4%) had mild or moderate illnesses. Age of 50 years or older, breathing problems, diarrhea, and longer time between the first medical visit and admission were associated with higher level of clinical severity. Surveillance-identified cases were much less likely to progress to severe illness. Although the COVID-19 epidemic has been contained in Shenzhen, close monitoring and risk assessments are imperative for prevention and control of COVID-19 in future.