Dynamic Zero-Covid strategy curtails mutagenesis and emergence of new variants of the SARS-CoV-2 (preprint)

Within the local outbreak period of SARS-CoV-2 Delta variant in Nanjing and Yangzhou, China, we analyzed the mutation process of the Delta variants in 520 cases, as well as the production, spread and elimination of new mutant strains under the non-pharmaceutical interventions (NPI) strategy. The investigation on distribution of COVID-19 cases and phylogenetic analysis of SARS-CoV-2 genome sequences attributed to tracking the transmission chains, transmission chains were terminated by the isolation of the COVID-19 patients and quarantine of close-contracts, suggesting the importance of NPI in prompting some mutations to disappear and stopping the transmission of new variants. Dynamic zero-Covid strategy has been implemented successfully to against the second-largest local epidemic caused by an imported COVID-19 case in China.

Effectiveness of inactive COVID-19 vaccines against severe illness in B.1.617.2 (Delta) variant-infected patients in Jiangsu, China (preprint)

The SARS-CoV-2 B.1.617.2 (Delta) variant has caused a new surge in the number of COVID-19 cases. The effectiveness of vaccines against this variant is not fully understood. Using data from a recent large-scale outbreak of COVID-19 in China, we conducted a real-world study to explore the effect of inactivated vaccine immunization on the course of disease in patients infected with Delta variants. We recruited 476 confirmed cases over the age of 18, of which 42 were severe. After adjusting for age, gender, and comorbidities, patients who received two doses of inactivated vaccine (fully vaccinated) had an 88% reduced risk in progressing to the severe stage (adjusted OR: 0.12, 95% CI: 0.02- 0.45). However, this protective effect was not observed in patients who only received only one dose of the vaccine(adjusted OR: 1.11, 95% CI: 0.51- 2.36). The full immunization offered 100% protection from a severe illness among women. The effect of the vaccine was potentially affected by underlying medical conditions (OR: 0.26, 95% CI: 0.03-1.23). This is the largest real-world study confirming the effectiveness of inactive COVID-19 vaccines against severe illness in Delta variant-infected patients in Jiangsu, China.

High viral load suggests increased COVID-19 severity in a longitudinal cohort (preprint)

Background: An outbreak caused by the 2019 novel coronavirus (2019-nCoV) has spread globally. However, the viral dynamics, co-infection and their associations with clinical severity, have not been well explored.Methods: We longitudinally enrolled 23 (Five severe-type, ten common-type and eight asymptomatic-type patients) hospitalized 2019-nCov-infected patients in Jiangsu between January 21 and February 11, 2020. Medical records and pharyngeal swab specimens, were collected to analyze the association between viral dynamic and disease severity.Results: Five severe-type, ten common-type and eight asymptomatic-type patients were enrolled. Linear mixed effects models revealed that the common and severe-type patients had a higher level of viral load (3.08 points, 95% CI, 0.51-5.65, P = 0.019; 6.07 points, 95% CI, 2.79-9.35, P < 0.001) and maintained a higher peak viral load ( P = 0.066 and 0.022, respectively), when compared with the asymptomatic group. Viral load shedding among older patients (aged ≥ 60) processed slower than that among younger patients ( P = 0.047). RNA virome sequencing identified two co-infected RNA viruses, Human endogenous retrovirus H (HERV) and Human picobirnavirus (HPBV). Of note, HPBV was detected in one severe-type and two common-type patients, while was not detected in all the asymptomatic cases.Conclusion: Higher viral load was positively associated with disease severity. This finding highlights the importance of monitoring the viral kinetics to identify patients at greater risk of progressing to severe pneumonia.

A SARS-CoV-2 surrogate virus neutralization test (sVNT) based on antibody-mediated blockage of ACE2-spike (RBD) protein-protein interaction (preprint)

At this critical moment of the international response to the COVID-19 outbreak, there is an urgent need for a robust serological test to detect neutralizing antibodies to SARS-CoV-2. Such a test is not only important for contact tracing, but for determining infection rate, herd immunity and predicted humoral protection. The current gold standard is a virus neuralization test (VNT) requiring live virus and a biosafety level 3 (BSL3) laboratory. On the other hand, the ELISA- or lateral flow-based assays are for the detection of binding antibodies, which does not directly correlate with their neutralizing ability. Here we report a SARS-CoV-2 surrogate virus neutralization test (sVNT) that is designed to detect total neutralizing antibodies in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of virus-host interaction between the ACE2 receptor protein and the receptor binding domain (RBD) of the viral spike protein. The test has been validated with two COVID-19 patient cohorts in two different countries, achieving 100% specificity and 95-100% sensitivity and is capable of differentiating antibody responses from other known human coronaviruses. Importantly, the sVNT does not require BSL3 containment, thereby making the test immediately accessible to the global community.

A rare symptom of ofactory dysfunction in coronavirus disease 2019: report of three cases (preprint)

Three patients of coronavirus disease (COVID-19) showed the symptoms of olfactory dysfunction. Clinical characteristics and treatment were retrospective analyzed. Olfactory disorders are uncommon symptoms of COVID-19. Early diagnosis and intervention are key to the recovery of olfactory disorders. Particular attention should be devoted to rare symptoms of COVID-19. 

Characterization of a big family cluster infection associated with SARS-Cov-2 in Nanjing district (preprint)

Background: Outbreak of COVID-19 has brought catastrophe to huge numbers of families. However, even though numerous tragedies occurred, there were few reports about family cluster infection in the academic journals. Methods: The electronic medical records of 10 COVID-19 patients in a big family were retrospectively reviewed and analyzed.Results: These 10 patients, 4 males and 6 females, were infected through two successive family feasts during Spring Festival. The infection source was a family member at asymptomatic state, who lived in Hubei but travelled to Nanjing. The median age of these 10 patients was 61.5, with the oldest 95 and youngest 38. The incubation period varied from 3 to 17 days, with the median of 5.5. Of them, 2 patients were asymptomatic. The most common symptoms at onset were fever (6/10) and dry cough (6/10). All of them displayed lesions on the chest CT. 40% of them had leukopenia, neutropenia and lymphopenia. After anti-virus treatment, all the patients significantly improved and were discharged. Conclusions: SARS-Cov-2 was highly contagious and so crafty that a varied incubation period did exist. Part of patients might be asymptomatic, which was the potential source of transmission. More measures for protection or quarantine should be taken at home if family member had travel history nearby the epidemic area. 

Characterization of a big family cluster infection associated with SARS-Cov-2 in Nanjing district (preprint)

Background: Outbreak of COVID-19 has brought catastrophe to huge numbers of families. However, even though numerous tragedies occurred, there were few reports about family cluster infection in the academic journals. Methods: The electronic medical records of 10 COVID-19 patients in a big family were retrospectively reviewed and analyzed. Results: These 10 patients, 4 males and 6 females, were infected through two successive family feasts during Spring Festival. The infection source was a family member at asymptomatic state, who lived in Hubei but travelled to Nanjing. The median age of these 10 patients was 61.5, with the oldest 95 and youngest 38. The incubation period varied from 3 to 17 days, with the median of 5.5. Of them, 2 patients were asymptomatic. The most common symptoms at onset were fever (6/10) and dry cough (6/10). All of them displayed lesions on the chest CT. 40% of them had leukopenia, neutropenia and lymphopenia. After anti-virus treatment, all the patients significantly improved and were discharged. Conclusions: SARS-Cov-2 was highly contagious and so crafty that a varied incubation period did exist. Part of patients might be asymptomatic, which was the potential source of transmission. More measures for protection or quarantine should be taken at home if family member had travel history nearby the epidemic area. Keywords: COVID-19, SARS-Cov-2, family cluster, asymptomatic, incubation period.

Epidemiological and clinical characteristics of COVID-19 patients in Nanjing (preprint)

Background: Since December 2019, the outbreak of COVID-19 has spread quickly and thumped many countries and regions. The epidemic of central China was under the spotlight and attracted much more attentions. However, there are few reports describing COVID-19 patients in the regions outside of Wuhan, which are undergoing the change from sporadic imported cases to community-acquired transmission.Methods: The electronic medical records of 74 laboratory-confirmed patients of COVID-19 were retrospectively reviewed and analyzed. Their epidemiological, demographic, clinical and radiological characteristics were systematically summarized. The difference between severe patients and non-severe patients were also analyzed statistically.Results: The 74 COVID-19 patients were composed of 4 (5.4%) mild patients, 56 (75.7%) common patients, 13 (17.6%) severe patients and 1 (1.4%) critical patient. 43 were male, and 31 were female, with the average age 48.1±17.5. No significant difference of susceptibility was observed between genders, and almost people with all age were susceptible to SARS-CoV-2 infection. Before Jan 26, only imported sporadic cases were observed. However, from that day onward, family cluster infection cases increased dramatically, up to 70.3% (52/74), which were mainly from 15 family. The incubation period spanned from 0 to 19 days, with the median 5, and 81.4% had symptom onset within 7 days. At admission, 31.1% of patients had underlying diseases and the most common underlying diseases were hypertension (13.5%) and diabetes (5.4%). The most common symptoms were fever (90.5%), cough (75.7%), fatigue (36.5%) and chest distress (32.4%). 36.5% and 16.2% of patients had leukopenia and lymphocytopenia. 43.2% of patients had increased C reactive protein (CRP), and 40.5% had higher erythrocyte sedimentation rate (ESR) and 21.6% had higher calcitonin. 74.3% of patients had obvious lesions in both lung lobes and 56.8% of lesions manifested as ground glass opacity. Compared with non-severe group, the severe/critical group were significantly older and had more underlying diseases. After treatment, all patients improved and were discharged. No medical professional infection and death case were reported.Conclusion: The epidemic of COVID-19 in Nanjing were mainly caused by family cluster infection. The entire prevalence and illness were much milder than those of Wuhan. The disease of COVID-19 could be controlled and cured.  

Comparative study of the lymphocyte change between COVID-19 and non-COVID-19 pneumonia cases suggesting uncontrolled inflammation might not be the main reason of tissue injury (preprint)

Background: The corona virus disease 2019 (COVID-19) shows unusually high transmission rate and unique clinical characteristics, with key pathological mechanism remaining unclear. Here, we analysed the laboratory data based on clinical samples from COVID-19 patients, in parallel comparison with non-COVID-19 pneumonia cases, in an attempt to elucidate the key pathological features of COVID-19 during its infection of the human body. Methods: We analysed biochemical indices and lymphocyte subpopulation in COVID-19 patients, and compare these data from non-COVID-19 pneumonia cases. Correlation analysis was performed between leukocyte subgroups count and biochemical indexes in COVID-19 patients. Results: The study enrolled 110 patients, comprising 88 COVID-19 patients and 22 non-COVID-19 pneumonia cases. We observed significant differences, including abnormal biochemical indices (CRP, LDH, AST, eGFR, and sodium ion concentration) and reduced lymphocyte subsets count, between the COVID-19 patients and non-COVID-19-caused pneumonia cases. Correlation analysis indicates that the count for lymphocyte subsets-but not that for neutrophils and monocytes-exhibits a significant negative correlation with biochemical indices relating to organ injury, in the COVID-19 infected patients. Conclusions: The study indicates significantly different clinical features between 2019 novel coronavirus (2019-nCoV)-caused and non-2019-nCoV-caused pneumonia, especially in terms of lymphocytopenia and organ injury. Notably, correlation analysis demonstrates that tissue damage in COVID-19 patients is attributed to virus infection itself rather than uncontrolled inflammatory responses ("cytokine storm"). These findings provide new insights for developing efficient therapeutic strategies against COVID-19 infection.

Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing, China (preprint)

Background: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Methods: Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. Findings: None of the 24 asymptomatic cases presented any obvious symptoms before nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue and etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and five (20.8%) presented stripe shadowing in the lungs. The remaining seven (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These seven cases were younger (median age: 14.0 years; P = 0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Interpretation: The asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.