Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS: 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION: The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING: Shenzhen Science and Technology Programs.

Hospital Strain and COVID-19 Fatality - England, April 2020-March 2022.

What is already known about this topic?: During the coronavirus disease 2019 (COVID-19) pandemic, tremendous efforts have been made in countries to suppress epidemic peaks and strengthen hospital services to avoid hospital strain and ultimately reduce the risk of death from COVID-19. However, there is limited empirical evidence that hospital strain increases COVID-19 deaths. What is added by this report?: We found the risk of death from COVID-19 was linearly associated with the number of patients currently in hospitals, a measure of hospital strain, before the Omicron period. This risk could be increased by a maximum of 188.0%. What are the implications for public health practice?: These findings suggest that any (additional) effort to reduce hospital strain would be beneficial during early large COVID-19 outbreaks and possibly also others alike. During an Omicron outbreak, vigilance remains necessary to prevent excess deaths caused by hospital strain as happened in Hong Kong Special Administrative Region, China.

Characteristics and Containment of 74 Imported COVID-19 Outbreaks: Experiences, Lessons, and Implications - China, 2020-2021.

What is already known about this topic?: After the initial coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, the outbreaks during the dynamic-zero policy period in the mainland of China have not been systematically documented. What is added by this report?: We summarized the characteristics of 74 imported COVID-19 outbreaks between March 19, 2020 and December 31, 2021. All outbreaks of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were successfully contained with the aid of nucleic acid testing, modern communication technologies, and non-pharmacological interventions. What are the implications for public health practice?: These findings provide us with confidence for the containment of future emerging infectious diseases alike at early stages to prevent pandemics or to win time to gain experience, develop vaccines and drugs, vaccinate people, and wait for the possible lessening of the virus' pathogenicity.

Correction: SARS-CoV-2 infection in China-Before the pandemic.

[This corrects the article DOI: 10.1371/journal.pntd.0008472.].

The COVID-19 pandemic and the future of public health

The COVID-19 pandemic provides us with a rare opportunity to deeply examine the validity of the construction of modern medicine, which is armed by science, and focus more on technologies than on people?s values and more on new ideas than on conventional wisdom. The world?s responses to the COVID-19 emergency have revealed a badly weakened public health system ? one of the three pillars of medicine, the other two being basic medicine and clinical medicine. A 100 years ago, public health was the only effective measure for combating infectious diseases, which were then the main cause of human death. It is still a decisive weapon against COVID-19 and other communicable diseases alike, but was barely recognized and trusted at the beginning of the pandemic by the general public and even some international strategists. However, the epidemic has been effectively contained in China by non-pharmacological public health measures, which saved valuable time for the development of vaccines in the country and probably hundreds of thousands of lives as well. Public health aims to improve the health of the entire population by using societal methods. It is not simply a medical issue, and building a strong public health system requires broad participation from various sections of society.

Contact Settings and Risk for Transmission in 3410 Close Contacts of Patients With COVID-19 in Guangzhou, China : A Prospective Cohort Study.

BACKGROUND: Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated. OBJECTIVE: To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings. DESIGN: Prospective cohort study. SETTING: Close contacts of persons infected with SARS-CoV-2 in Guangzhou, China. PARTICIPANTS: 3410 close contacts of 391 index cases were traced between 13 January and 6 March 2020. Data on the setting of the exposure, reverse transcriptase polymerase chain reaction testing, and clinical characteristics of index and secondary cases were collected. MEASUREMENT: Coronavirus disease 2019 (COVID-19) cases were confirmed by guidelines issued by China. Secondary attack rates in different settings were calculated. RESULTS: Among 3410 close contacts, 127 (3.7% [95% CI, 3.1% to 4.4%]) were secondarily infected. Of these 127 persons, 8 (6.3% [CI, 2.1% to 10.5%]) were asymptomatic. Of the 119 symptomatic cases, 20 (16.8%) were defined as mild, 87 (73.1%) as moderate, and 12 (10.1%) as severe or critical. Compared with the household setting (10.3%), the secondary attack rate was lower for exposures in health care settings (1.0%; odds ratio [OR], 0.09 [CI, 0.04 to 0.20]) and on public transportation (0.1%; OR, 0.01 [CI, 0.00 to 0.08]). The secondary attack rate increased with the severity of index cases, from 0.3% (CI, 0.0% to 1.0%) for asymptomatic to 3.3% (CI, 1.8% to 4.8%) for mild, 5.6% (CI, 4.4% to 6.8%) for moderate, and 6.2% (CI, 3.2% to 9.1%) for severe or critical cases. Index cases with expectoration were associated with higher risk for secondary infection (13.6% vs. 3.0% for index cases without expectoration; OR, 4.81 [CI, 3.35 to 6.93]). LIMITATION: There was potential recall bias regarding symptom onset among patients with COVID-19, and the symptoms and severity of index cases were not assessed at the time of exposure to contacts. CONCLUSION: Household contact was the main setting for transmission of SARS-CoV-2, and the risk for transmission of SARS-CoV-2 among close contacts increased with the severity of index cases. PRIMARY FUNDING SOURCE: Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme.

SARS-CoV-2 infection in China-Before the pandemic.

In order to rapidly inform polices in the international response to the ongoing pandemic of coronavirus disease 19 (COVID-19), we summarize in this review current evidence on epidemiological and clinical features of the infection, transmission routes, problems of nucleic-acid testing, the epidemiological trend in China and impact of interventional measures, and some lessons learned. We concluded that the epidemic is containable with traditional nonpharmacological interventions, mainly through social distancing and finding and isolating suspected patients and close contacts. Nonpharmacological interventions are the only effective measures currently accessible and have suppressed some 90% of the infections in China. Close contacts are the major mechanism of transmission, which makes it possible to control this epidemic through nonpharmacological methods. Nucleic-acid testing alone may miss some 50% of infected patients, and other methods such as chest computerized tomography (CT) or serology should be considered to supplement molecular testing. The development of vaccines and drugs is important, but hesitation to make use of nonpharmacological interventions may mean missing golden opportunities for effective actions.

Implementation of Clinical Diagnostic Criteria and Universal Symptom Survey Contributed to Lower Magnitude and Faster Resolution of the COVID-19 Epidemic in Wuhan.

The majority of cases infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China centered in the city of Wuhan. Despite a rapid increase in the number of cases and deaths due to the coronavirus disease 2019 (COVID-19), the epidemic was stemmed via a combination of epidemic mitigation and control measures. This study evaluates how the implementation of clinical diagnostics and universal symptom surveys contributed to epidemic control in Wuhan. We extended the susceptibles-exposed-infectious-removed (SEIR) transmission dynamics model by considering three quarantined compartments (SEIR+Q). The SEIR+Q dynamics model was fitted using the daily reported number of confirmed infections and unconfirmed cases by clinical diagnostic criteria up to February 14, 2020, in Wuhan. Applying the model to carry forward the pre-February 14 trend in Wuhan, the number of daily new diagnosed cases would be expected to drop below 100 by March 25, below 10 by April 29, and reach 0 by May 31, 2020. The observed case counts after February 14 demonstrated that the daily new cases fell below 100 by March 6, below 10 by March 11, and reached 0 by March 18, respectively, 19, 49, and 74 d earlier than model predictions. By March 30, the observed number of cumulative confirmed cases was 50 006, which was 19 951 cases fewer than the predicted count. Effective reproductive number R(t) analysis using observed frequencies showed a remarkable decline after the implementation of clinical diagnostic criteria and universal symptom surveys, which was significantly below the R(t) curve estimated by the model assuming that the pre-February 14 trend was carried forward. In conclusion, the proposed SEIR+Q dynamics model was a good fit for the epidemic data in Wuhan and explained the large increase in the number of infections during February 12-14, 2020. The implementation of clinical diagnostic criteria and universal symptom surveys contributed to a contraction in both the magnitude and the duration of the epidemic in Wuhan.

Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding.

We report epidemiological and clinical investigations on ten pediatric SARS-CoV-2 infection cases confirmed by real-time reverse transcription PCR assay of SARS-CoV-2 RNA. Symptoms in these cases were nonspecific and no children required respiratory support or intensive care. Chest X-rays lacked definite signs of pneumonia, a defining feature of the infection in adult cases. Notably, eight children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative, raising the possibility of fecal-oral transmission.