Transmission dynamics of SARS-CoV-2 Omicron variant infections in Hangzhou, Zhejiang, China, January-February 2022.

OBJECTIVES: We aimed to explore the transmission dynamics of the Omicron BA.1.1 variant in an outbreak in China. METHODS: We constructed 113 transmission pairs based on the time of exposure and symptom onset for identified infectors and infectees, using the epidemiological data collected during an outbreak in Hangzhou, Zhejiang province, China, between January and February 2022. The key epidemiological parameters were estimated. RESULTS: The mean estimates of the incubation period and latent period distributions were 3.8 days (95% credible interval: 3.5, 4.1) and 3.1 days (2.8, 3.5), respectively. The overall transmission risk peaked at symptom onset, and we estimated that 33.6% (24.8, 42.5) of transmission occurred before symptom onset. The forward generation time decreased from 5.2 days (4.7, 5.7) at the start of the outbreak to 2.2 days (2.0, 2.5) by the end. Allowing this variation over time in the generation time distribution, we estimated that the reproduction number dropped rapidly from 9.5 (3.5, 18.4) to 0.8 (0.3, 1.5) over the outbreak. CONCLUSION: Shorter incubation period and latent period were estimated for the Omicron BA.1.1 variant. Stringent public health measures prevented a large epidemic by reducing transmission, as indicated by the shortened generation time.

Analysis of epidemic characteristics of forty-two COVID-19 cluster outbreaks in Hangzhou

Objective: To determine the epidemic characteristics of forty-two coronavirus disease 2019 (COVID-19) cluster outbreaks in Hangzhou city and provide scientific evidence for further prevention and control measures.

Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody.

An essential step for SARS-CoV-2 infection is the attachment to the host cell receptor by its Spike receptor-binding domain (RBD). Most of the existing RBD-targeting neutralizing antibodies block the receptor-binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non-RBM-targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a KD of 5.6 nM, neutralizes SARS-CoV-2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross-reactivity against SARS-CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted "ideal" vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20-binding but confers little or no resistance to neutralization. Finally, in vitro mode-of-action characterization and negative-stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS-CoV-2 Spike for the development of potential antiviral drugs.

Retrospective study of risk factors of 43 patients with severe coronavirus disease 2019 pneumonia

Objective To explore the risk factors of 43 patients with severe coronavirus disease 2019 pneumonia(COVID-19) in Hangzhou. Methods The clinical and epidemiological data of COVID-19 confirmed patients during 1 st January 2020 and 20 th March 2020 in Hangzhou were collected.The risk factors of the severe cases were analyzed by univariate and multivariate logistic regression. Results Up to 20 th March 2020,a total of 169 patients were reported in Hangzhou, among which, 43(25.44%) were severe cases.The analysis showed that over 60 years old[χ~2=6.16,P=0.01;OR(95%CI)=3.35(1.29-8.69)],hypertension[χ~2=6.91,P<0.001;OR(95%CI)=3.80(1.40-10.28)],headache as initial onset symptom [χ~2=4.80,P=0.03;OR(95%CI)=3.02(1.12-8.09)] and delayed hospitalization(Z=-2.21,P=0.03) were statistically significant. Conclusions Age over 60 years, hypertension, headache as initial onset symptom are risk factors and delayed hospitalization is influencing factor of severe COVID-19 patients.It is necessary to monitor COVID-19 patients′ condition and take effective treatment timely.

Analysis of risk factors in 43 severely ill patients with novel coronavirus pneumonia

Objective: To investigate the risk factors of 43 patients with severe novel coronavirus pneumonia (coronavirusdisease-19, COVID-19) in Hangzhou.

Rapid genomic characterization of SARS-CoV-2 viruses from clinical specimens using nanopore sequencing.

The novel SARS-CoV-2 outbreak has swiftly spread worldwide. The rapid genome sequencing of SARS-CoV-2 strains has become a helpful tool for better understanding the genomic characteristics and origin of the virus. To obtain virus whole-genome sequences directly from clinical specimens, we performed nanopore sequencing using a modified ARTIC protocol in a portable nanopore sequencer and validated a routine 8-h workflow and a 5-h rapid pipeline. We conducted some optimization to improve the genome sequencing workflow. The sensitivity of the workflow was also tested by serially diluting RNA from clinical samples. The optimized pipeline was finally applied to obtain the whole genomes of 29 clinical specimens collected in Hangzhou from January to March 2020. In the 29 obtained complete genomes of SARS-CoV-2, 33 variations were identified and analyzed. The genomic variations and phylogenetic analysis hinted at multiple sources and different transmission patterns during the COVID-19 epidemic in Hangzhou, China. In conclusion, the genomic characteristics and origin of the virus can be quickly determined by nanopore sequencing following our workflows.

Potential transmission of SARS-CoV-2 on a flight from Singapore to Hangzhou, China: An epidemiological investigation.

BACKGROUND: Between January 24, 2020 and February 15, 2020, an outbreak of COVID-19 occurred among 335 passengers on a flight from Singapore to Hangzhou in China. This study aimed to investigate the source of the outbreak and assess the risk of transmission of COVID-19 during the flight. METHOD: Using a standardized questionnaire, we collected information on the travelers' demographic characteristics and illness before, during, and after the flight. We also collected data on factors potentially associated with COVID-19 transmission during the flight. RESULTS: A total of 16 COVID-19 patients were diagnosed among all passengers; the overall attack rate was 4.8%. The attack rate among passengers who had departed from Wuhan was significantly higher than that among those who had departed from other places. One passenger without an epidemiological history of exposure before boarding developed COVID-19. During the flight, he was seated near four infected passengers from Wuhan for approximately an hour and did not wear his facemask correctly during the flight. CONCLUSIONS: COVID-19 transmission may have occurred during the flight. However, the majority of the cases in the flight-associated outbreak could not be attributed to transmission on the flight but were associated with exposure to the virus in Wuhan or to infected members in a single tour group.

Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China.

Importance: Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. Objective: To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. Design, Setting, and Participants: This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. Main Outcomes and Measures: SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Results: Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Conclusions and Relevance: In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.

Development and Validation of a Nomogram for Assessing Survival in Patients With COVID-19 Pneumonia.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide and continues to threaten peoples' health as well as put pressure on the accessibility of medical systems. Early prediction of survival of hospitalized patients will help in the clinical management of COVID-19, but a prediction model that is reliable and valid is still lacking. METHODS: We retrospectively enrolled 628 confirmed cases of COVID-19 using positive RT-PCR tests for SARS-CoV-2 in Tongji Hospital, Wuhan, China. These patients were randomly grouped into a training (60%) and a validation (40%) cohort. In the training cohort, LASSO regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of patients with COVID-19. A nomogram based on the 3 variables was built for clinical use. AUCs, concordance indexes (C-index), and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts. RESULTS: Hypertension, higher neutrophil-to-lymphocyte ratio, and increased NT-proBNP values were found to be significantly associated with poorer prognosis in hospitalized patients with COVID-19. The 3 predictors were further used to build a prediction nomogram. The C-indexes of the nomogram in the training and validation cohorts were 0.901 and 0.892, respectively. The AUC in the training cohort was 0.922 for 14-day and 0.919 for 21-day probability of in-hospital survival, while in the validation cohort this was 0.922 and 0.881, respectively. Moreover, the calibration curve for 14- and 21-day survival also showed high coherence between the predicted and actual probability of survival. CONCLUSIONS: We built a predictive model and constructed a nomogram for predicting in-hospital survival of patients with COVID-19. This model has good performance and might be utilized clinically in management of COVID-19.