Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns

Abstract: This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic could have been favored by specific weather conditions and other factors. It is found that the 2020 winter weather in the region of Wuhan (Hubei, Central China)-where the virus first broke out in December and spread widely from January to February 2020-was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic broke out from February to March. The statistical analysis was extended to cover the United States of America, which overtook Italy and China as the country with the highest number of confirmed COronaVIrus Disease 19 (COVID-19) cases, and then to the entire world. The found correlation patterns suggest that the COVID-19 lethality significantly worsens (4 times on average) under weather temperatures between 4 ∘ C and 12 ∘ C and relative humidity between 60% and 80%. Possible co-factors such as median population age and air pollution were also investigated suggesting an important influence of the former but not of the latter, at least, on a synoptic scale. Based on these results, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From February to March, the 4-12 ∘ C isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, optimally coinciding with the geographic regions most affected by the pandemic from February to March. It is predicted that in the spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted colder southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year and because of the lower median age of their population. Google-Earth-Pro interactive-maps covering the entire world are provided as supplementary files.


Statistical analysis of the impact of environmental temperature on the exponential growth rate of cases infected by COVID-19

Abstract: We perform a statistical analysis for understanding the effect of the environmental temperature on the exponential growth rate of the cases infected by COVID-19 for US and Italian regions. In particular, we analyze the datasets of regional infected cases, derive the growth rates for regions characterized by a readable exponential growth phase in their evolution spread curve and plot them against the environmental temperatures averaged within the same regions, derive the relationship between temperature and growth rate, and evaluate its statistical confidence. The results clearly support the first reported statistically significant relationship of negative correlation between the average environmental temperature and exponential growth rates of the infected cases. The critical temperature, which eliminates the exponential growth, and thus the COVID-19 spread in US regions, is estimated to be TC = 86.1 ± 4.3 F0.


Asymmetric nexus between temperature and COVID-19 in the top ten affected provinces of China: A current application of quantile-on-quantile approach

Abstract: The present study examines the asymmetrical effect of temperature on COVID-19 (Coronavirus Disease) from 22 January 2020 to 31 March 2020 in the 10 most affected provinces in China. This study used the Sim & Zhou' quantile-on-quantile (QQ) approach to analyze how the temperature quantities affect the different quantiles of COVID-19. Daily COVID-19 and, temperature data collected from the official websites of the Chinese National Health Commission and Weather Underground Company (WUC) respectively. Empirical results have shown that the relationship between temperature and COVID-19 is mostly positive for Hubei, Hunan, and Anhui, while mostly negative for Zhejiang and Shandong provinces. The remaining five provinces Guangdong, Henan, Jiangxi, Jiangsu, and Heilongjiang are showing the mixed trends. These differences among the provinces can be explained by the differences in the number of COVID-19 cases, temperature, and the province's overall hospital facilitations. The study concludes that maintaining a safe and comfortable atmosphere for patients while COVID-19 is being treated may be rational.


Maximum Daily Temperature, Precipitation, Ultra-Violet Light and Rates of Transmission of SARS-Cov-2 in the United States

Abstract: BACKGROUND: Previous reports have suggested that transmission of SARS-CoV-2 is reduced by higher temperatures and higher humidity. We analyzed case-data from the United States to investigate effects of temperature, precipitation, and UV Light on community transmission of SARS-CoV-2. METHODS: Daily reported cases of SARS-CoV-2 across the United States from 01/22/2020 to 04/03/2020 were analyzed. We used negative binomial regression modelling to investigate whether daily maximum temperature, precipitation, UV Index and the incidence 5 days later were related. We performed sensitivity analyses at 3 days, 7 days and 9 days to assess transmission lags. RESULTS: A maximum temperature greater than 52°F on a given day was associated with a lower rate of new cases at 5 days[IRR: 0.85(0.76,0.96)p=0.009]. Among observations with daily temperatures below 52°F, there was a significant inverse association between the maximum daily temperature and the rate of cases at 5 days [IRR 0.98(0.97,0.99)p=0.001]. The rate of new cases was predicted to be lower for theoretical states that maintained a stable maximum daily temperature above 52°F with a predicted 23-fewer cases per-million per-day by 25 days of the epidemic. A 1-unit higher UV index was associated with a lower rate at 5 days [IRR 0.97(0.95,0.99)p=0.004]. Precipitation was not associated with a greater rate of cases at 5 days [IRR 0.98(0.89,1.08)p=0.65]. CONCLUSION: The incidence of disease declines with increasing temperature up until 52°F and is lower at warmer versus cooler temperatures. However, the association between temperature and transmission is small and transmission is likely to remain high at warmer temperatures.


The Weather Impacts the Outbreak of COVID-19 in Mainland China

Abstract: Recent literature has suggested that climate conditions have considerably significant influences on the transmission of coronavirus COVID-19. However, there is a lack of comprehensive study that investigates the relationships between multiple weather factors and the development of COVID-19 pandemic while excluding the impact of social factors. In this paper, we study the relationships between six main weather factors and the infection statistics of COVID-19 on 250 cities in Mainland China. Our correlation analysis using weather and infection statistics indicates that all the studied weather factors are correlated with the spread of COVID-19, where precipitation shows the strongest correlation. We also build a weather-aware predictive model that forecasts the number of infected cases should there be a second wave of the outbreak in Mainland China. Our predicted results show that cities located in different geographical areas are likely to be challenged with the second wave of COVID-19 at very different time periods and the severity of the outbreak varies to a large degree, in correspondence with the varying weather conditions.


Anomalous atmospheric circulation favored the spread of COVID-19 in Europe

Abstract: The current pandemic caused by the coronavirus SARS-CoV-2 is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. It has subsequently spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, in terms of air temperature and humidity, in Italy and Spain for a quicker spread of the virus compared with the rest of the European countries. It seems plausible that the strong atmospheric stability and associated dry conditions that dominated in these regions may have favored the virus's propagation, by short-range droplet transmission as well as likely by long-range aerosol (airborne) transmission.


Evidence that high temperatures and intermediate relative humidity might favor the spread of COVID-19 in tropical climate: A case study for the most affected Brazilian cities

Abstract: This study aimed to analyze how meteorological conditions such as temperature, humidity and rainfall can affect the spread of COVID-19 in five Brazilian (São Paulo, Rio de Janeiro, Brasília, Manaus and Fortaleza) cities. The cities selected were those with the largest number of confirmed cases considering data of April 13. Variables such as number of cumulative cases, new daily cases and contamination rate were employed for this study. Our results showed that higher mean temperatures and average relative humidity favored the COVID-19 transmission, differently from reports from coldest countries or periods of time under cool temperatures. Thus, considering the results obtained, intersectoral policies and actions are necessary, mainly in cities where the contamination rate is increasing rapidly. Thus, prevention and protection measures should be adopted in these cities aiming to reduce transmission and the possible collapse of the health system.


Association between climate variables and global transmission oF SARS-CoV-2

Abstract: In this study, we aimed at analyzing the associations between transmission of and deaths caused by SARS-CoV-2 and meteorological variables, such as average temperature, minimum temperature, maximum temperature, and precipitation. Two outcome measures were considered, with the first aiming to study SARS-CoV-2 infections and the second aiming to study COVID-19 mortality. Daily data as well as data on SARS-CoV-2 infections and COVID-19 mortality obtained between December 1, 2019 and March 28, 2020 were collected from weather stations around the world. The country's population density and time of exposure to the disease were used as control variables. Finally, a month dummy variable was added. Daily data by country were analyzed using the panel data model. An increase in the average daily temperature by one degree Fahrenheit reduced the number of cases by approximately 6.4 cases/day. There was a negative correlation between the average temperature per country and the number of cases of SARS-CoV-2 infections. This association remained strong even with the incorporation of additional variables and controls (maximum temperature, average temperature, minimum temperature, and precipitation) and fixed country effects. There was a positive correlation between precipitation and SARS-CoV-2 transmission. Countries with higher rainfall measurements showed an increase in disease transmission. For each average inch/day, there was an increase of 56.01 cases/day. COVID-19 mortality showed no significant association with temperature.


Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries

Abstract: The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 °C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.


A mechanism-based parameterisation scheme to investigate the association between transmission rate of COVID-19 and meteorological factors on plains in China

Abstract: The novel coronavirus disease 2019 (COVID-19), which first emerged in Hubei province, China, has become a pandemic. However, data regarding the effects of meteorological factors on its transmission are limited and inconsistent. A mechanism-based parameterisation scheme was developed to investigate the association between the scaled transmission rate (STR) of COVID-19 and the meteorological parameters in 20 provinces/municipalities located on the plains in China. We obtained information on the scale of population migrated from Wuhan, the world epicentre of the COVID-19 outbreak, into the study provinces/municipalities using mobile-phone positioning system and big data techniques. The highest STRs were found in densely populated metropolitan areas and in cold provinces located in north-eastern China. Population density had a non-linear relationship with disease spread (linearity index, 0.9). Among various meteorological factors, only temperature was significantly associated with the STR after controlling for the effect of population density. A negative and exponential relationship was identified between the transmission rate and the temperature (correlation coefficient, -0.56; 99% confidence level). The STR increased substantially as the temperature in north-eastern China decreased below 0 °C (the STR ranged from 3.5 to 12.3 when the temperature was between -9.41 °C and -13.87 °C), whilst the STR showed less temperature dependence in the study areas with temperate weather conditions (the STR was 1.21 ± 0.57 when the temperature was above 0 °C). Therefore, a higher population density was linearly whereas a lower temperature (<0 °C) was exponentially associated with an increased transmission rate of COVID-19. These findings suggest that the mitigation of COVID-19 spread in densely populated and/or cold regions will be a great challenge.


Effect of weather on COVID-19 spread in the US: A prediction model for India in 2020

Abstract: The effect of weather on COVID-19 spread is poorly understood. Recently, few studies have claimed that warm weather can possibly slowdown the global pandemic, which has already affected over 1.6 million people worldwide. Clarification of such relationships in the worst affected country, the US, can be immensely beneficial to understand the role of weather in transmission of the disease in the highly populated countries, such as India. We collected the daily data of new cases in 50 US states between Jan 1-Apr 9, 2020 and also the corresponding weather information (i.e., temperature (T) and absolute humidity (AH)). Distribution modeling of new cases across AH and T, helped identify the narrow and vulnerable AH range. We validated the results for 10-day intervals against monthly observations, and also worldwide trends. The results were used to predict Indian regions which would be vulnerable to weather based spread in upcoming months of 2020. COVID-19 spread in the US is significant for states with 4 < AH < 6 g/m3 and number of new cases > 10,000, irrespective of the chosen time intervals for study parameters. These trends are consistent with worldwide observations, but do not correlate well with India so far possibly due the total cases reported per interval < 10,000. The results clarify the relationship between weather parameters and COVID-19 spread. The vulnerable weather parameters will help classify the risky geographic areas in different countries. Specifically, with further reporting of new cases in India, prediction of states with high risk of weather based spread will be apparent.


Short-term effects of specific humidity and temperature on COVID-19 morbidity in select US cities

Abstract: Little is known about the environmental conditions that drive the spatiotemporal patterns of SARS-CoV-2. Preliminary research suggests an association with meteorological parameters. However, the relationship with temperature and humidity is not yet apparent for COVID-19 cases in US cities first impacted. The objective of this study is to evaluate the association between COVID-19 cases and meteorological parameters in select US cities. A case-crossover design with a distributed lag nonlinear model was used to evaluate the contribution of ambient temperature and specific humidity on COVID-19 cases in select US cities. The case-crossover examines each COVID case as its own control at different time periods (before and after transmission occurred). We modeled the effect of temperature and humidity on COVID-19 transmission using a lag period of 7 days. A subset of 8 cities were evaluated for the relationship with meteorological parameters and 5 cities were evaluated in detail. Short-term exposure to humidity was positively associated with COVID-19 transmission in 4 cities. The associations were small with 3 out of 4 cities exhibiting higher COVID19 transmission with specific humidity that ranged from 6 to 9 g/kg. Our results suggest that weather should be considered in infectious disease modeling efforts. Future work is needed over a longer time period and across different locations to clearly establish the weather-COVID19 relationship.


Impact of meteorological factors on the COVID-19 transmission: A multi-city study in China

Abstract: The purpose of the present study is to explore the associations between novel coronavirus disease 2019 (COVID-19) case counts and meteorological factors in 30 provincial capital cities of China. We compiled a daily dataset including confirmed case counts, ambient temperature (AT), diurnal temperature range (DTR), absolute humidity (AH) and migration scale index (MSI) for each city during the period of January 20th to March 2nd, 2020. First, we explored the associations between COVID-19 confirmed case counts, meteorological factors, and MSI using non-linear regression. Then, we conducted a two-stage analysis for 17 cities with more than 50 confirmed cases. In the first stage, generalized linear models with negative binomial distribution were fitted to estimate city-specific effects of meteorological factors on confirmed case counts. In the second stage, the meta-analysis was conducted to estimate the pooled effects. Our results showed that among 13 cities that have less than 50 confirmed cases, 9 cities locate in the Northern China with average AT below 0 °C, 12 cities had average AH below 4 g/m3, and one city (Haikou) had the highest AH (14.05 g/m3). Those 17 cities with 50 and more cases accounted for 90.6% of all cases in our study. Each 1 °C increase in AT and DTR was related to the decline of daily confirmed case counts, and the corresponding pooled RRs were 0.80 (95% CI: 0.75, 0.85) and 0.90 (95% CI: 0.86, 0.95), respectively. For AH, the association with COVID-19 case counts were statistically significant in lag 07 and lag 014. In addition, we found the all these associations increased with accumulated time duration up to 14 days. In conclusions, meteorological factors play an independent role in the COVID-19 transmission after controlling population migration. Local weather condition with low temperature, mild diurnal temperature range and low humidity likely favor the transmission.


Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil

Abstract: The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have robustly identified a relationship between temperature and the number of cases. However, there is no specific study for a tropical climate such as Brazil. This work aims to determine the relationship of temperature to COVID-19 infection for the state capital cities of Brazil. Cumulative data with the daily number of confirmed cases was collected from February 27 to April 1, 2020, for all 27 state capital cities of Brazil affected by COVID-19. A generalized additive model (GAM) was applied to explore the linear and nonlinear relationship between annual average temperature compensation and confirmed cases. Also, a polynomial linear regression model was proposed to represent the behavior of the growth curve of COVID-19 in the capital cities of Brazil. The GAM dose-response curve suggested a negative linear relationship between temperatures and daily cumulative confirmed cases of COVID-19 in the range from 16.8 °C to 27.4 °C. Each 1 °C rise of temperature was associated with a -4.8951% (t = -2.29, p = 0.0226) decrease in the number of daily cumulative confirmed cases of COVID-19. A sensitivity analysis assessed the robustness of the results of the model. The predicted R-squared of the polynomial linear regression model was 0.81053. In this study, which features the tropical temperatures of Brazil, the variation in annual average temperatures ranged from 16.8 °C to 27.4 °C. Results indicated that temperatures had a negative linear relationship with the number of confirmed cases. The curve flattened at a threshold of 25.8 °C. There is no evidence supporting that the curve declined for temperatures above 25.8 °C. The study had the goal of supporting governance for healthcare policymakers.


Projections for COVID-19 pandemic in India and effect of temperature and humidity

Abstract: BACKGROUND AND AIMS: As, the COVID-19 has been deemed a pandemic by World Health Organization (WHO), and since it spreads everywhere throughout the world, investigation in relation to this disease is very much essential. Investigation of pattern in the occurrence of COVID-19, to check the influence of different meteorological factors on the incidence of COVID-19 and prediction of incidence of COVID-19 are the objectives of this paper. METHODS: For trend analysis, Sen's Slope and Man-Kendall test have been used, Generalized Additive Model (GAM) of regression has been used to check the influence of different meteorological factors on the incidence and to predict the frequency of COVID-19, and Verhulst (Logistic) Population Model has been used. RESULTS: Statistically significant linear trend found for the daily-confirmed cases of COVID-19. The regression analysis indicates that there is some influence of the interaction of average temperature (AT) and average relative humidity (ARH) on the incidence of COVID-19. However, this result is not consistent throughout the study area. The projections have been made up to 21st May, 2020. CONCLUSIONS: Trend and regression analysis give an idea of the incidence of COVID-19 in India while projection made by Verhulst (Logistic) Population Model for the confirmed cases of the study area are encouraging as the sample prediction is as same as the actual number of confirmed COVID-19 cases.


Development of an Assessment Method for Investigating the Impact of Climate and Urban Parameters in Confirmed Cases of COVID-19: A New Challenge in Sustainable Development

Abstract: Sustainable development has been a controversial global topic, and as a complex concept in recent years, it plays a key role in creating a favorable future for societies. Meanwhile, there are several problems in the process of implementing this approach, like epidemic diseases. Hence, in this study, the impact of climate and urban factors on confirmed cases of COVID-19 (a new type of coronavirus) with the trend and multivariate linear regression (MLR) has been investigated to propose a more accurate prediction model. For this propose, some important climate parameters, including daily average temperature, relative humidity, and wind speed, in addition to urban parameters such as population density, were considered, and their impacts on confirmed cases of COVID-19 were analyzed. The analysis was performed for three case studies in Italy, and the application of the proposed method has been investigated. The impacts of parameters have been considered with a delay time from one to nine days to find out the most suitable combination. The result of the analysis demonstrates the effectiveness of the proposed model and the impact of climate parameters on the trend of confirmed cases. The research hypothesis approved by the MLR model and the present assessment method could be applied by considering several variables that exhibit the exact delay of them to new confirmed cases of COVID-19.


Factors determining the diffusion of COVID-19 and suggested strategy to prevent future accelerated viral infectivity similar to COVID

Abstract: This study has two goals. The first is to explain the geo-environmental determinants of the accelerated diffusion of COVID-19 that is generating a high level of deaths. The second is to suggest a strategy to cope with future epidemic threats similar to COVID-19 having an accelerated viral infectivity in society. Using data on sample of N = 55 Italian province capitals, and data of infected individuals at as of April 7th, 2020, results reveal that the accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution of cities measured with days exceeding the limits set for PM10 (particulate matter 10 µm or less in diameter) or ozone. In particular, hinterland cities with average high number of days exceeding the limits set for PM10 (and also having a low wind speed) have a very high number of infected people on 7th April 2020 (arithmetic mean is about 2200 infected individuals, with average polluted days greater than 80 days per year), whereas coastal cities also having days exceeding the limits set for PM10 or ozone but with high wind speed have about 944.70 average infected individuals, with about 60 average polluted days per year; moreover, cities having more than 100 days of air pollution (exceeding the limits set for PM10), they have a very high average number of infected people (about 3350 infected individuals, 7th April 2020), whereas cities having less than 100 days of air pollution per year, they have a lower average number of infected people (about 1014 individuals). The findings here also suggest that to minimize the impact of future epidemics similar to COVID-19, the max number of days per year that Italian provincial capitals or similar industrialized cities can exceed the limits set for PM10 or for ozone, considering their meteorological conditions, is about 48 days. Moreover, results here reveal that the explanatory variable of air pollution in cities seems to be a more important predictor in the initial phase of diffusion of viral infectivity (on 17th March 2020, b1 = 1.27, p < 0.001) than interpersonal contacts (b2 = 0.31, p < 0.05). In the second phase of maturity of the transmission dynamics of COVID-19, air pollution reduces intensity (on 7th April 2020 with b'1 = 0.81, p < 0.001) also because of the indirect effect of lockdown, whereas regression coefficient of transmission based on interpersonal contacts has a stable level (b'2 = 0.31, p < 0.01). This result reveals that accelerated transmission dynamics of COVID-19 is due to mainly to the mechanism of "air pollution-to-human transmission" (airborne viral infectivity) rather than "human-to-human transmission". Overall, then, transmission dynamics of viral infectivity, such as COVID-19, is due to systemic causes: general factors that are the same for all regions (e.g., biological characteristics of virus, incubation period, etc.) and specific factors which are different for each region and/or city (e.g., complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity) and health level of individuals (habits, immune system, age, sex, etc.). Lessons learned for COVID-19 in the case study here suggest that a proactive strategy to cope with future epidemics is also to apply especially an environmental and sustainable policy based on reduction of levels of air pollution mainly in hinterland and polluting cities- (having low wind speed, high percentage of moisture and number of fog days) -that seem to have an environment that foster a fast transmission dynamics of viral infectivity in society. Hence, in the presence of polluting industrialization in regions that can trigger the mechanism of air pollution-to-human transmission dynamics of viral infectivity, this study must conclude that a comprehensive strategy to prevent future epidemics similar to COVID-19 has to be also designed in environmental and socioeconomic terms, that is also based on sustainability science and environmental science, and not only in terms of biology, medicine, healthcare and health sector.


Impact of temperature on the dynamics of the COVID-19 outbreak in China

Abstract: A COVID-19 outbreak emerged in Wuhan, China at the end of 2019 and developed into a global pandemic during March 2020. The effects of temperature on the dynamics of the COVID-19 epidemic in China are unknown. Data on COVID-19 daily confirmed cases and daily mean temperatures were collected from 31 provincial-level regions in mainland China between Jan. 20 and Feb. 29, 2020. Locally weighted regression and smoothing scatterplot (LOESS), distributed lag nonlinear models (DLNMs), and random-effects meta-analysis were used to examine the relationship between daily confirmed cases rate of COVID-19 and temperature conditions. The daily number of new cases peaked on Feb. 12, and then decreased. The daily confirmed cases rate of COVID-19 had a biphasic relationship with temperature (with a peak at 10 °C), and the daily incidence of COVID-19 decreased at values below and above these values. The overall epidemic intensity of COVID-19 reduced slightly following days with higher temperatures with a relative risk (RR) was 0.96 (95% CI: 0.93, 0.99). A random-effect meta-analysis including 28 provinces in mainland China, we confirmed the statistically significant association between temperature and RR during the study period (Coefficient = -0.0100, 95% CI: -0.0125, -0.0074). The DLNMs in Hubei Province (outside of Wuhan) and Wuhan showed similar patterns of temperature. Additionally, a modified susceptible-exposed-infectious-recovered (M-SEIR) model, with adjustment for climatic factors, was used to provide a complete characterization of the impact of climate on the dynamics of the COVID-19 epidemic.


Arctic Oscillation: possible trigger of COVID-19 outbreak

Abstract: The current COVID-19 pandemic is having detrimental consequences worldwide. The pandemic started to develop strongly by the end of January and beginning of February 2020, first in China with subsequent rapid spread to other countries with new epicenters of the outbreaks concentrated mainly within the 30-50 degrees North latitudinal band (e.g., South Korea, Japan, Iran, Italy, Spain). Simultaneously, an unusual persistent anticyclonic situation prevailing at latitudes around 40 degrees North was observed on global scale, in line with an anomalously strong positive phase of the Arctic Oscillation. This atypical situation could have resulted in favorable meteorological conditions for a quicker spread of the virus over the latitude band detailed above. This possible connection needs further attention in order to understand the meteorological and climatological factors related to the COVID-19 outbreak, and for anticipating the spatio-temporal distribution of possible future pandemics.


Assessing the relationship between ground levels of ozone (O3) and nitrogen dioxide (NO2) with coronavirus (COVID-19) in Milan, Italy

Abstract: This paper investigates the correlation between the high level of coronavirus SARS-CoV-2 infection accelerated transmission and lethality, and surface air pollution in Milan metropolitan area, Lombardy region in Italy. For January-April 2020 period, time series of daily average inhalable gaseous pollutants ozone (O3) and nitrogen dioxide (NO2), together climate variables (air temperature, relative humidity, wind speed, precipitation rate, atmospheric pressure field and Planetary Boundary Layer) were analyzed. In spite of being considered primarily transmitted by indoor bioaerosols droplets and infected surfaces or direct human-to-human personal contacts, it seems that high levels of urban air pollution, and climate conditions have a significant impact on SARS-CoV-2 diffusion. Exhibited positive correlations of ambient ozone levels and negative correlations of NO2 with the increased rates of COVID-19 infections (Total number, Daily New positive and Total Deaths cases), can be attributed to airborne bioaerosols distribution. The results show positive correlation of daily averaged O3 with air temperature and inversely correlations with relative humidity and precipitation rates. Viral genome contains distinctive features, including a unique N-terminal fragment within the spike protein, which allows coronavirus attachment on ambient air pollutants. At this moment it is not clear if through airborne diffusion, in the presence of outdoor and indoor aerosols, this protein "spike" of the new COVID-19 is involved in the infectious agent transmission from a reservoir to a susceptible host during the highest nosocomial outbreak in some agglomerated industrialized urban areas like Milan is. Also, in spite of collected data for cold season (winter-early spring) period, when usually ozone levels have lower values than in summer, the findings of this study support possibility as O3 can acts as a COVID-19 virus incubator. Being a novel pandemic coronavirus version, it might be ongoing during summer conditions associated with higher air temperatures, low relative humidity and precipitation levels.


Prioritizing and Analyzing the Role of Climate and Urban Parameters in the Confirmed Cases of COVID-19 Based on Artificial Intelligence Applications

Abstract: Nowadays, an infectious disease outbreak is considered one of the most destructive effects in the sustainable development process. The outbreak of new coronavirus (COVID-19) as an infectious disease showed that it has undesirable social, environmental, and economic impacts, and leads to serious challenges and threats. Additionally, investigating the prioritization parameters is of vital importance to reducing the negative impacts of this global crisis. Hence, the main aim of this study is to prioritize and analyze the role of certain environmental parameters. For this purpose, four cities in Italy were selected as a case study and some notable climate parameters-such as daily average temperature, relative humidity, wind speed-and an urban parameter, population density, were considered as input data set, with confirmed cases of COVID-19 being the output dataset. In this paper, two artificial intelligence techniques, including an artificial neural network (ANN) based on particle swarm optimization (PSO) algorithm and differential evolution (DE) algorithm, were used for prioritizing climate and urban parameters. The analysis is based on the feature selection process and then the obtained results from the proposed models compared to select the best one. Finally, the difference in cost function was about 0.0001 between the performances of the two models, hence, the two methods were not different in cost function, however, ANN-PSO was found to be better, because it reached to the desired precision level in lesser iterations than ANN-DE. In addition, the priority of two variables, urban parameter, and relative humidity, were the highest to predict the confirmed cases of COVID-19.


Susceptible supply limits the role of climate in the early SARS-CoV-2 pandemic

Abstract: Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios based on known coronavirus biology. We find that while variations in weather may be important for endemic infections, during the pandemic stage of an emerging pathogen the climate drives only modest changes to pandemic size. A preliminary analysis of non-pharmaceutical control measures indicates that they may moderate the pandemic-climate interaction via susceptible depletion. Our findings suggest, without effective control measures, strong outbreaks are likely in more humid climates and summer weather will not substantially limit pandemic growth.


T cells found in coronavirus patients 'bode well' for long-term immunity.


A 219-mer CHO-expressing receptor-binding domain of SARS-CoV S protein induces potent immune responses and protective immunity.

Abstract: Development of vaccines is essential for the prevention of future recurrences of severe acute respiratory syndrome (SARS), caused by the SARS coronavirus (SARS-CoV). The spike (S) protein, especially receptor-binding domain (RBD) of SARS-CoV, plays important roles in the prevention of SARS infection, and is thus an important component in SARS vaccine development. In this study, we expressed a 219-mer (residues 318-536) RBD protein in Chinese hamster ovary (CHO)-K1 cells (RBD219-CHO), and tested its immune responses and protective immunity in a mouse model. The results showed that this recombinant protein was correctly folded, being able to maintain intact conformation and authentic antigenicity. It could induce strong humoral and cellular immune responses and high titers of neutralizing antibodies in the vaccinated mice. RBD219-CHO protein elicited potent protective immunity that protected all vaccinated mice from SARS-CoV challenge. These results suggest that the recombinant RBD219-CHO protein has great potential for the development of an effective and safe SARS subunit vaccine.


The perplexing question of trained immunity versus adaptive memory in COVID-19.

Abstract: The wide spectrum of symptoms observed in COVID-19 appears to defy explanation. Apart from geographic limitation to people with prior exposure to other coronaviruses and air pollutants, inflammatory comordidities and older ages are also among the main factors of susceptibility to severe illness. The unusual epidemiological data pointed out in children and African territories have revealed new insights in host-pathogen interplay with more focus on epigenetic regulation of cognitive compartments belonging to innate immunity. Should trained immunity be proven to be involved in timely immune responsiveness against SARS-CoV-2 and that adaptive memory could be detrimental, both treatment regimens and vaccine design will tremendously change accordingly with more focus on upper respiratory tissue innate immunity to subdue this threat underway. This article is protected by copyright. All rights reserved.


The laboratory tests and host immunity of COVID-19 patients with different severity of illness.

Abstract: BACKGROUND The Coronavirus Disease-2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak in China. The host immunity of COVID-19 patients is unknown. METHODS The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS A total of 65 SARS-CoV-2-positive patients were classified as mild (n=30), severe (n=20), and extremely severe (n=15) illness. Many routine laboratory tests such as ferritin, lactate dehydrogenase and D-dimer were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells and B cells were all gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The co-stimulatory molecule CD28 had opposite results. The percentage of natural regulatory T cells was decreased in extremely severe patients. The percentage of IFN-γ producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ producing CD4+ T cells was increased in extremely severe patients. The IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients. CONCLUSIONS The number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.


A phased lift of control: a practical strategy to achieve herd immunity against Covid-19 at the country level

Abstract: Most countries are affected by the Covid-19 pandemic and experience rapidly increasing numbers of cases and deaths. Many have implemented nationwide stringent control to avoid overburdening the health care system. This paralyzes economic and social activities until the availability of a vaccine, which may take years. We propose an alternative exit strategy to develop herd immunity in a predictable and controllable way: a phased lift of control. This means that successive parts of the country (e.g. provinces) stop stringent control, and Covid-19-related IC admissions are distributed over the country as the whole. Importantly, vulnerable individuals need to be shielded until herd immunity has developed in their area. We explore the characteristics and duration of this strategy using a novel individual-based model for geographically stratified transmission of Covid-19 in a country. The model predicts that individuals will have to experience stringent control for about 14 months on average, but this duration may be significantly shortened by future developments (more IC beds, better drugs). Clearly, the strategy will have a profound impact on individuals and society, and should therefore be considered carefully by various other disciplines (e.g. health systems, ethics, economics) before actual implementation.


Can the protection be among us? Previous viral contacts and prevalent HLA alleles could be avoiding an even more disseminated COVID-19 pandemic.

Abstract: Background: COVID-19 is bringing scenes of sci-fi movies into real life, and it seems to be far from over. Infected individuals exhibit variable severity, with no relation between the number of cases and mortality, suggesting the involvement of the populational genetic constitution and previous cross-reactive immune contacts in the individuals' disease outcome. Methods: A clustering approach was conducted to investigate the involvement of human MHC alleles with individuals' outcomes. HLA frequencies from affected countries were used to fuel the Hierarchical Clusterization Analysis. The formed groups were compared regarding their death rates. To prospect the T cell targets in SARS-CoV-2, and by consequence, the epitopes that are conferring cross-protection in the current pandemic, we modeled 3D structures of HLA-A*02:01 presenting immunogenic epitopes from SAR-CoV-1, recovered from Immune Epitope Database. These pMHC structures were also compared with models containing the corresponding SARS-CoV-2 epitope, with alphacoronavirus sequences, and with a panel of immunogenic pMHC structures contained in CrossTope. Findings: The combined use of HLA-B*07, HLA-B*44, HLA-DRB1*03, and HLADRB1*04 allowed the clustering of affected countries presenting similar death rates, based only on their allele frequencies. SARS-CoV HLA-A*02:01 epitopes were structurally investigated. It reveals molecular conservation between SARS-CoV-1 and SARS-CoV-2 peptides, enabling the use of formerly SARS-CoV-1 experimental epitopes to inspect actual targets that are conferring cross-protection. Alpha-CoVs and, impressively, viruses involved in human infections share fingerprints of immunogenicity with SARS-CoV peptides. Interpretation: Wide-scale HLA genotyping in COVID-19 patients shall improve prognosis prediction. Structural identification of previous triggers paves the way for herd immunity examination and wide spectrum vaccine development. Funding: This work was supported by the National Council for Scientific and Technological Development (CNPq) and National Council for the Improvement of Higher Education (CAPES) for their support


Immunity Passports for SARS-CoV-2: an online experimental study of the impact of antibody test terminology on perceived risk and behaviour

Abstract: Objective: To assess the impact of describing an antibody-positive test result using the terms Immunity and Passport or Certificate, alone or in combination, on perceived risk of becoming infected with SARS-CoV-2 and intention to continue protective behaviours. Design: 2 by 3 experimental design. Setting: Online with data collected between 28th April and 1st May 2020. Participants: 1,204 adults registered with a UK research panel. Intervention: Participants were randomised to receive one of six descriptions of an antibody test and results showing SARS-CoV-2 antibodies, differing in the terms used to describe the type of test (Immunity vs Antibody) and the test result (Passport vs Certificate vs Test). Main outcome measures: The primary outcome was the proportion of participants perceiving no risk of becoming infected with SARS-CoV-2 given an antibody positive test result. Other outcomes include intended changes to frequency of hand washing and physical distancing. Results: When using the term Immunity (vs Antibody), 19.1% of participants [95% CI: 16.1 to 22.5] (vs 9.8% [95% CI: 7.5 to 12.4]) perceived no risk of catching coronavirus at some point in the future given an antibody-positive test result (AOR: 2.91 [95% CI: 1.52 to 5.55]). Using the terms Passport or Certificate, as opposed to Test, had no significant effect (AOR: 1.24 [95% CI: 0.62 to 2.48] and AOR: 0.96 [95% CI: 0.47 to 1.99] respectively). There was no significant interaction between the effects of the test and result terminology. Across groups, perceiving no risk of infection was associated with an intention to wash hands less frequently (AOR: 2.32 [95% CI: 1.25 to 4.28]) but there was no significant association with intended avoidance of physical contact with others outside of the home (AOR: 1.37 [95% CI: 0.93 to 2.03]). Conclusions: Using the term Immunity (vs Antibody) to describe antibody tests for SARS-CoV-2 increases the proportion of people believing that an antibody-positive result means they have no risk of catching coronavirus in the future, a perception that may be associated with less frequent hand washing. The way antibody testing is described may have implications for the likely impact of testing on transmission rates.


Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus.

Abstract: The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin.


Children's vaccines do not induce cross reactivity against SARS-CoV.

Abstract: In contrast with adults, children infected by severe acute respiratory syndrome-corona virus (SARS-CoV) develop milder clinical symptoms. Because of this, it is speculated that children vaccinated with various childhood vaccines might develop cross immunity against SARS-CoV. Antisera and T cells from mice immunised with various vaccines were used to determine whether they developed cross reactivity against SARS-CoV. The results showed no marked cross reactivity against SARS-CoV, which implies that the reduced symptoms among children infected by SARS-CoV may be caused by other factors.


Antibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus-associated illnesses

Abstract: Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme-linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43 HCoV-associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥60 years) and 28 (65%) in 28 younger adults (aged 21-40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections.


COVID-19 is milder in children possibly due to cross-immunity


New IgM seroconversion and positive RT-PCR test after exposure to the virus in recovered COVID-19 patient


Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2

Abstract: Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.


SARS-CoV-2 antibody testing-questions to be asked

Abstract: Severe acute respiratory syndrome coronavirus 2 infection and development of coronavirus disease 2019 presents a major health care challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against severe acute respiratory syndrome coronavirus 2, presents a major cornerstone in handling the pandemic. Currently, there is an increase in demand for antibody testing and a large number of tests are already marketed or are in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross-reactivity and cross-protectivity, the diagnostic value of antibodies of different isotypes, and the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article, the recently established COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues on the basis of currently available data sets in this rapidly moving field.


Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review

Abstract: Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least 7 coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms. Those that infect animals can evolve and become infectious to humans. Three recent examples of these viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19). COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 20 May 2020 show more than 5 million people had been infected with the virus, causing more than 330,000 deaths in over 210 countries worldwide. The large amount of information received daily relating to COVID-19 is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).


SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

Abstract: The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.


Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge

Abstract: Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50-66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.


Multiplex detection and dynamics of IgG antibodies to SARS-CoV2 and the highly pathogenic human coronaviruses SARS-CoV and MERS-CoV

Abstract: BACKGROUND: Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic. METHODS: We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay. RESULTS: On samples collected ≥14 days after symptoms onset, the accuracy of the assay is 100 % (95 % CI: 100-100) for the Spike antigen and 99.9 % (95 % CI:99.7-100) for NC. By logistic regression, we estimated that 50 % of the patients have seroconverted at 5.7 ± 1.6; 5.7 ± 1.8 and 7.9 ± 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100 % with SARS-CoV1 NC. Twenty-nine of the 36 (80.5 %) samples tested were positive by the commercial ELISA while 31/36 (86.1 %) were positive by the novel assay. CONCLUSIONS: Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.


Will we see protection or reinfection in COVID-19?


Dissecting antibody-mediated protection against SARS-CoV-2


Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2

Abstract: Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen A [HLA-A], -B, and -C genes) may affect susceptibility to and severity of the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We performed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome was successfully sampled and was represented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting that individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (M. Lin, H.-T. Tseng, J. A. Trejaut, H.-L. Lee, et al., BMC Med Genet 4:9, 2003, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting that it could enable cross-protective T-cell-based immunity. Finally, we reported global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic.IMPORTANCE Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.


Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS

Abstract: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed "original antigenic sin." The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.


Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?

Abstract: Trained immunity is a type of non-specific memory-like immune response induced by some pathogens and vaccines, such as BCG, which can confer antigen-independent protection against a wide variety of pathogens. The BCG vaccine has been extensively used to protect against tuberculosis for almost a 100 years. Interestingly, this vaccine reduces children's mortality caused by infections unrelated to Mycobacterium tuberculosis infection, a phenomenon thought to be due to the induction of trained immunity. The SARS-CoV-2 pandemic has infected, as of April 22, 2020, 2,623,231 people globally, causing a major public health problem worldwide. Currently, no vaccine or treatment is available to control this pandemic. We analyzed the number of positive cases and deaths in different countries and correlated them with the inclusion of BCG vaccination at birth in their national vaccination programs. Interestingly, those countries where BCG vaccination is given at birth have shown a lower contagion rate and fewer COVID-19-related deaths, suggesting that this vaccine may induce trained immunity that could confer some protection for SARS-CoV-2.


Development of passive immunity against SARS-CoV-2 for management of immunodeficient patients - a perspective


Grundlagen der Replikation und der Immunologie von SARS-CoV-2

Abstract: Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T‑cell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.


The immunity induced by recombinant spike proteins of SARS coronavirus in Balb/c mice

Abstract: The immune effect of two recombinant protein fragments of spike protein in severe acute respiratory syndrome coronavirus (SARS CoV) was investigated in Balb/c mice. Two partial spike gene fragments S1 (322 1464 bp) and S2 (2170 2814 bp) of SARS coronavirus were amplified by RT-PCR, and cloned into pET-23a prokaryotic expression vector, then transformed into competent Escherichia E. coli BL21 (DE3)(pLysS) respectively. Recombinant proteins were expressed and purified by Ni(2+) immobilized metal ion affinity chromatography. The purified proteins mixed with complete Freund adjuvant were injected into Balb/c mice three times at a two-week interval. High titer antibody was detected in the serum of immunized Balb/c mice, and mice immunized with S1 protein produced high titer IgG1, IgG2a, IgG2b and IgG3, while those immunized with S2 protein produced high titer IgG1, IgG2a, but lower titer IgG2b and IgG3. Serum IFN-concentration was increased significantly but the concentrations of Il-2, IL-4 and IL-10 had no significant change. And a marked increase was observed in the number of spleen CD8+ T cells. The results showed that recombinant proteins of SARS coronavirus spike protein induced hormonal and cellular immune response in Balb/c mice.


Immunodominant viral peptides as determinants of cross-reactivity in the immune system – Can we develop wide spectrum viral vaccines?

Abstract: Summary When we look back to Edward Jenner vaccination of a young man in 1796, we cannot help thinking that he was both lucky and crazy. Crazy because he decided to test in a human being a hypothesis based mainly in the traditional belief that people who had acquired cowpox from the udders of a cow were thereafter resistant to smallpox, a quite devastating disease, and lucky because (even considering that he did not know this at that time) he succeeded to induce protection against a pathogen through the induction of an immune response directed against a different agent. Not only was he able to protect the young man but he took the first step towards the development of a vast new field, vaccination. It is acceptable to say that Jenner was lucky because he succeeded in promoting protection against smallpox using a cowpox virus and this induction of protection in a cross-reactive way is believed to be quite rare. Nevertheless, more and more examples of cross-reactive immune responses are being described and we are beginning to admit that cross-reactivity is far more common and important than we used to think. Here we review cross-reactivity in the immune system and the plasticity of T cell recognition. Based on the existence of T cell receptor promiscuous recognition and cross-recognition of conserved viral immunodominant epitopes, we propose two approaches to develop wide spectrum viral vaccines. The first one is based on the identification, characterization, and cloning of immunodominant viral epitopes able to stimulate responses against different viruses. The produced peptides could then be purified and serve as a basis for vaccine therapies. A second strategy is based on the identification of conserved patterns in immunodominant viral peptides and the production of synthetic peptides containing the amino acid residues necessary for MHC anchoring and TCR contact. Although we are still far from a complete knowledge of the cross-reactivity phenomenon in the immune system, the analysis of immunodominant viral epitopes and the identification of particular “viral patterns” seems to be important steps towards the development of wide spectrum viral vaccines.


Coronavirus and PARP expression dysregulate the NAD Metabolome: a potentially actionable component of innate immunity

Abstract: SARS-CoV-2 is a coronavirus (CoV) and cause of COVID-19, which is much more lethal in older people and those with comorbid conditions for unknown reasons. Innate immune responses to CoVs are initiated by recognition of double-stranded RNA and induction of interferon, which turns on a gene expression program that inhibits viral replication. Here we show that SARS-CoV-2 infection of cells, ferrets and a person strikingly dysregulates the NAD gene set by inducing a set of PARP family members that includes enzymes required for the innate immune response to CoVs. CoV infection also induces a severe attack on host cell NAD. Overexpression of one induced enzyme, PARP10, is sufficient to depress host NAD. Gene expression and pharmacological data suggest that boosting NAD through the nicotinamide and nicotinamide riboside kinase pathways may restore antiviral PARP functions to support innate immunity to CoVs, whereas PARP1,2 inhibition does not restore PARP10 activity.


Potential biases arising from epidemic dynamics in observational seroprotection studies

Abstract: The extent and duration of immunity following SARS-CoV-2 infection are critical outstanding questions about the epidemiology of this novel virus, and studies are needed to evaluate the effects of serostatus on reinfection. Understanding the potential sources of bias and methods to alleviate biases in these studies is important for informing their design and analysis. Confounding by individual-level risk factors in observational studies like these is relatively well appreciated. Here, we show how geographic structure and the underlying, natural dynamics of epidemics can also induce noncausal associations. We take the approach of simulating serologic studies in the context of an uncontrolled or a controlled epidemic, under different assumptions about whether prior infection does or does not protect an individual against subsequent infection, and using various designs and analytic approaches to analyze the simulated data. We find that in studies assessing the efficacy of serostatus on future infection, comparing seropositive individuals to seronegative individuals with similar time-dependent patterns of exposure to infection, by stratifying or matching on geographic location and time of enrollment, is essential to prevent bias.


Anatomical features of anti-viral immunity in the respiratory tract

Abstract: Abstract The mucosal surfaces of the lungs are a major portal of entry for virus infections and there are urgent needs for new vaccines that promote effective pulmonary immunity. However, we have only a rudimentary understanding of the requirements for effective cellular immunity in the respiratory tract. Recent studies have revealed that specialized cellular immune responses and lymphoid tissues are involved in the protection of distinct anatomical microenvironments of the respiratory tract, such as the large airways of the nose and the alveolar airspaces. This review discusses some of the anatomical features of anti-viral immunity in the respiratory tract including the role of local lymphoid tissues and the relationship between effector and memory T cells in the airways, the lung parenchyma, and lymphoid organs.


DNA Vaccine Encoding Middle East Respiratory Syndrome Coronavirus S1 Protein Induces Protective Immune Responses in Mice

Abstract: The Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging pathogen that continues to cause outbreaks in the Arabian peninsula and in travelers from this region, raising the concern that a global pandemic could occur. Here, we show that a DNA vaccine encoding the first 725 amino acids (S1) of MERS-CoV spike (S) protein induces antigen-specific humoral and cellular immune responses in mice. With three immunizations, high titers of neutralizing antibodies (up to 1: 10(4)) were generated without adjuvant. DNA vaccination with the MERS-CoV S1 gene markedly increased the frequencies of antigen-specific CD4(+) and CD8(+) T cells secreting IFN-γ and other cytokines. Both pcDNA3.1-S1 DNA vaccine immunization and passive transfer of immune serum from pcDNA3.1-S1 vaccinated mice protected Ad5-hDPP4-transduced mice from MERS-CoV challenge. These results demonstrate that a DNA vaccine encoding MERS-CoV S1 protein induces strong protective immune responses against MERS-CoV infection.


SARS-CoV-2, “common cold” coronaviruses’ cross-reactivity and “herd immunity”: The razor of Ockham (1285-1347)?


Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike

Abstract: The SARS-CoV-2 virus is responsible for the current worldwide coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoprotein of SARS-CoV-2 mediates viral entry and is the main target for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic and public health interventions. Here we performed a cross-sectional study on 98 SARS-CoV-2-infected individuals to evaluate humoral responses against the SARS-CoV-2 Spike. The vast majority of infected individuals elicited anti-Spike antibodies within 2 weeks after the onset of symptoms. The levels of receptor-binding domain (RBD)-specific IgG persisted overtime, while the levels of anti-RBD IgM decreased after symptoms resolution. Some of the elicited antibodies cross-reacted with other human coronaviruses in a genus-restrictive manner. While most of individuals developed neutralizing antibodies within the first two weeks of infection, the level of neutralizing activity was significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.


Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses

Abstract: Two zoonotic coronaviruses (CoV), SARS-CoV and MERS-CoV have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4(+) T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4(+) T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was interferon-γ-dependent and required early induction of robust innate and virus-specific CD8(+) T cell responses. The conserved epitope was also recognized in SARS-CoV and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4(+) T cells targeting conserved epitopes may have broad applicability in the context of new CoV and other respiratory virus outbreaks.


Will children reveal their secret? The coronavirus dilemma

Abstract: Epidemiological evidences show that SARS-CoV-2 infection in children is less frequent and severe than adults. Age-related ACE2 receptor expression, lymphocyte count and trained immunity might be the keystone to reveal children's secret.


A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2

Abstract: Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates. We estimate that if R(0) = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate.


Respiratory virus-induced heterologous immunity: Part of the problem or part of the solution?

Abstract: PURPOSE: To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination. METHODS: A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratory-virus induced adaptive HI. RESULTS: In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and influenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines which have the potential to provide protection against multiple virus strains are also discussed. Furthermore, respiratory viruses have been implicated in the development of autoimmune diseases, such as narcolepsy, Guillain–Barré syndrome, type 1 diabetes or myocarditis. Finally, we discuss the role of respiratory viruses in asthma and the hygiene hypothesis, and review our recent findings on HI between IV and allergens, which leads to protection from experimental asthma. CONCLUSION: Respiratory-virus induced HI may have protective but also detrimental effects on the host. Respiratory viral infections contribute to asthma or autoimmune disease development, but on the other hand, a lack of microbial encounter is associated with an increasing number of allergic as well as autoimmune diseases. Future research might help identify the elements which determine a protective or detrimental outcome in HI-based mechanisms.


Evaluating the promise of recombinant transmissible vaccines

Abstract: Transmissible vaccines have the potential to revolutionize infectious disease control by reducing the vaccination effort required to protect a population against a disease. Recent efforts to develop transmissible vaccines focus on recombinant transmissible vaccine designs (RTVs) because they pose reduced risk if intra-host evolution causes the vaccine to revert to its vector form. However, the shared antigenicity of the vaccine and vector may confer vaccine-immunity to hosts infected with the vector, thwarting the ability of the vaccine to spread through the population. We build a mathematical model to test whether a RTV can facilitate disease management in instances where reversion is likely to introduce the vector into the population or when the vector organism is already established in the host population, and the vector and vaccine share perfect cross-immunity. Our results show that a RTV can autonomously eradicate a pathogen, or protect a population from pathogen invasion, when cross-immunity between vaccine and vector is absent. If cross-immunity between vaccine and vector exists, however, our results show that a RTV can substantially reduce the vaccination effort necessary to control or eradicate a pathogen only when continuously augmented with direct manual vaccination. These results demonstrate that estimating the extent of cross-immunity between vector and vaccine is a critical step in RTV design, and that herpesvirus vectors showing facile reinfection and weak cross-immunity are promising.


SARS-CoV2 coronavirus: So far polite with children. Debatable immunological and non-immunological evidence

Abstract: Abstract The reasons for the relative resistance of children to certain infections such as that caused by coronavirus SARS- CoV2 are not yet fully clear. Deciphering these differences can provide important information about the pathogenesis of the disease. Regarding the SARS-CoV2 virus, children are at the same risk of infection as the general population of all ages, with the most serious cases being found in infants. However, it has been reported that the disease is much less frequent than in adults and that most cases are benign or moderate (even with high viral loads), provided there are no other risk factors or underlying diseases. It is not clear why they have lower morbidity and virtually no mortality. A series of findings, relationships and behavioral patterns between the infectious agent and the child host may account for the lower incidence and a greatly attenuated clinical presentation of the disease in children.


Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis

Abstract: PURPOSE: Previous studies assessing impact of acute respiratory distress syndrome (ARDS) on mortality have shown conflicting results. We sought to assess the independent association of ARDS with in-hospital mortality among intensive care unit (ICU) patients with sepsis. METHODS: We studied two prospective sepsis cohorts drawn from the Early Assessment of Renal and Lung Injury (EARLI; n = 474) and Validating Acute Lung Injury markers for Diagnosis (VALID; n = 337) cohorts. ARDS was defined by Berlin criteria. We used logistic regression to compare in-hospital mortality in patients with and without ARDS, controlling for baseline severity of illness. We also estimated attributable mortality, adjusted for illness severity by stratification. RESULTS: ARDS occurred in 195 EARLI patients (41%) and 99 VALID patients (29%). ARDS was independently associated with risk of hospital death in multivariate analysis, even after controlling for severity of illness, as measured by APACHE II (odds ratio [OR] 1.65 (95% confidence interval [CI] 1.02, 2.67), p = 0.04 in EARLI; OR 2.12 (CI 1.16, 3.92), p = 0.02 in VALID). Patients with severe ARDS (P/F < 100) primarily drove this relationship. The attributable mortality of ARDS was 27% (CI 14%, 37%) in EARLI and 37% (CI 10%, 51%) in VALID. ARDS was independently associated with ICU mortality, hospital length of stay (LOS), ICU LOS, and ventilator-free days. CONCLUSIONS: Development of ARDS among ICU patients with sepsis confers increased risk of ICU and in-hospital mortality in addition to other important outcomes. Clinical trials targeting patients with severe ARDS will be best poised to detect measurable differences in these outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06010-9) contains supplementary material, which is available to authorized users.


Infectious Atypical Pneumonia

Abstract: Infectious atypical pneumonia, also known as severe acute respiratory syndrome (SARS), is an acute respiratory infectious disease caused by SARS coronavirus (SARS-CoV). Clinically, it is characterized by fever, headache, muscular soreness, fatigue, dry cough rarely with phlegm, and diarrhea. Most patients experience accompanying pneumonia. In severe cases, the conditions may develop into acute lung injury, acute respiratory distress syndrome (ARDS), or even multiple organ failure that causes death. In China, SARS has been legally listed as one of the class B infectious diseases but is managed as class A infectious diseases, like anthrax and human infection of avian influenza.


Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction.

Abstract: AIMS Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly evolved into a sweeping pandemic. While its major manifestation is in the respiratory tract, the general extent of organ involvement as well as microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. METHODS This study reports autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. RESULTS The primary cause of death was respiratory failure with exudative diffuse alveolar damage with massive capillary congestion often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolisms (n=4), alveolar haemorrhage (n=3) and vasculitis (n=1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. CONCLUSIONS This study provides an overview of post-mortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates amongst these patients.


Covid-19: Death rate in England and Wales reaches record high because of covid-19.


Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury.

Abstract: The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75-7.48), p = 0.001; HR = 15.65 (95% CI = 2.43-100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p < 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.


Covid-19: risk factors for severe disease and death.


[Pathological changes of fatal coronavirus disease 2019 (COVID-19) in the lungs: report of 10 cases by postmortem needle autopsy].

Abstract: Objectives: To observe the pulmonary changes with coronavirus disease 2019 (COVID-19) in postmortem needle specimens, to detect the presence of 2019 novel coronavirus(2019-nCoV) in the lung tissues, and to analyze the clinicopathological characteristics. Methods: For 10 decedents with 2019-nCoV infection in Wuhan, bilateral lungs underwent ultrasound-guided percutaneous multi-point puncture autopsy, and pulmonary pathological changes were described in routine hematoxylin-eosin staining (HE) slides. Electron microscopy was also performed. The reverse transcription polymerase chain reaction (RT-PCR) was employed to detect 2019-nCoV nucleic acid in lung tissue, and the pathological characteristics were demonstrated in combination with clinical data analysis. Results: Of the 10 deaths associated with COVID-19, 7 were male and 3 were female. The average age was 70 (39-87) years. Medical record showed that 7 patients had underlying diseases. The average course of disease was 30 (16-36) days. Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. Type Ⅱ alveolar epithelial cells showed reactive hyperplasia and desquamation. Many macrophages accumulated in the alveolar cavity. Capillary hyaline thrombus and intravascular mixed thrombus were noted. In some cases, acute bronchiolitis with mucous membrane exfoliation, accumulation of bronchiolar secretions, and bronchiolar epithelial metaplasia occurred. In the cohort, a large number of bacteria (cocci) were detected in 1 case and a large number of fungi (yeast type) were detected in 1 case. Nine cases were positive for the nucleic acids of 2019-nCoV while one case remained negative by RT-PCR. Coronavirus particles were detected in the cytoplasm of type Ⅱ alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type Ⅱ alveolar epithelial cells. A large amount of neutrophils and monocytes infiltration is present in most cases and bacteria and fungi are detected in some cases, suggesting a serious bacterial or fungal infection secondary to the DAD.


Clinical characteristics of 82 cases of death from COVID-19.

Abstract: A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p = 0.002), alanine aminotransferase (p = 0.037) and time from initial symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.


Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography.

Abstract: AIMS Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19. METHODS AND RESULTS This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I > 20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th-75th percentile, 27-32) mm vs. 27.7 (25-30) mm, < 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02-1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02-1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, < 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27-3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO/FiO ratio on admission were other independent predictors for both myocardial injury and death. CONCLUSIONS An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death. TRANSLATIONAL PERSPECTIVE The present study identifies myocardial injury as a clinically relevant independent risk factor for death in the short term in a population of hospitalized patients with laboratory-confirmed COVID-19 outside of China undergoing chest computed tomography for suspected pneumonia on admission.The study also provides novel insights into the risk factors for myocardial injury, showing that an increased pulmonary artery diameter, assessed by chest computed tomography, is an independent predictor of myocardial injury as well as of mortality, suggesting that pulmonary circulation dysfunction is a pivotal pathological event with cardiac implications in COVID-19.