First reported from Wuhan, The People's Republic of China, on 31 December 2019, the ongoing outbreak of a novel coronavirus (2019‐nCoV) causes great global concerns. Based on the advice of the ...International Health Regulations Emergency Committee and the fact that to date 24 other countries also reported cases, the WHO Director‐General declared that the outbreak of 2019‐nCoV constitutes a Public Health Emergency of International Concern on 30 January 2020. Together with the other two highly pathogenic coronaviruses, the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), 2019‐nCov and other yet to be identified coronaviruses pose a global threat to public health. In this mini‐review, we provide a brief introduction to the pathology and pathogenesis of SARS‐CoV and MERS‐CoV and extrapolate this knowledge to the newly identified 2019‐nCoV.
Highlights
The pathology of SARS‐CoV and MERS‐CoV is introduced.
The pathogenesis of SARS‐CoV and MERS‐CoV is introduced.
The general features of 2019‐nCoV and the disease caused by it are described.
Long-term antibody responses and neutralizing activities in response to SARS-CoV-2 infection are not yet clear. Here we quantify immunoglobulin M (IgM) and G (IgG) antibodies recognizing the ...SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of 6 months from COVID-19 disease onset in 349 symptomatic COVID-19 patients who were among the first be infected world-wide. The positivity rate and magnitude of IgM-S and IgG-N responses increase rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset are associated with virus control and IgG-S titers correlate closely with the capacity to neutralize SARS-CoV-2. Although specific IgM-S/N become undetectable 12 weeks after disease onset in most patients, IgG-S/N titers have an intermediate contraction phase, but stabilize at relatively high levels over the 6 month observation period. At late time points, the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies are still >70%. These data indicate sustained humoral immunity in recovered patients who had symptomatic COVID-19, suggesting prolonged immunity.
Susceptibility of SARS-CoV-2 to UV irradiation Heilingloh, Christiane Silke; Aufderhorst, Ulrich Wilhelm; Schipper, Leonie ...
American journal of infection control,
10/2020, Letnik:
48, Številka:
10
Journal Article
Recenzirano
Odprti dostop
•SARS-CoV-2 is highly susceptible to irradiation with ultraviolet light.•High viral loads of 5 * 106 TCID50/ml SARS-CoV-2 can be inactivated in 9 minutes by UVC irradiation.•UVC irradiation ...represents a suitable disinfection method for SARS-CoV-2.
The coronavirus SARS-CoV-2 pandemic became a global health burden. We determined the susceptibility of SARS-CoV-2 to irradiation with ultraviolet light. The virus was highly susceptible to ultraviolet light. A viral stock with a high infectious titer of 5 × 106 TCID50/mL was completely inactivated by UVC irradiation after nine minutes of exposure. The UVC dose required for complete inactivation was 1,048 mJ/cm2. UVA exposure demonstrated only a weak effect on virus inactivation over 15 minutes. Hence, inactivation of SARS-CoV-2 by UVC irradiation constitutes a reliable method for disinfection purposes in health care facilities and for preparing SARS-CoV-2 material for research purpose.
Background:
Immune responses following vaccination against COVID-19 with different vaccines and the waning of immunity vary within the population. Genetic host factors are likely to contribute to ...this variability. However, to the best of our knowledge, no study on G protein polymorphisms and vaccination responses against COVID-19 has been published so far.
Methods:
Antibodies against the SARS-CoV-2 spike protein and T-cell responses against a peptide pool of SARS-CoV-2 S1 proteins were measured 1 and 6 months after the second vaccination with mRNA-1273 in the main study group of 204 participants. Additionally, antibodies against the SARS-CoV-2 spike protein were measured in a group of 597 participants 1 month after the second vaccination with mRNA-1273. Genotypes of
GNB3
c.825C>T were determined in all participants.
Results:
The median antibody titer against the SARS-CoV-2 spike protein and median values of spots increment in the SARS-CoV-2 IFN-γ ELISpot assay against the S1-peptide pool were significantly decreased from months 1 to 6 (
p
< 0.0001). Genotypes of
GNB3
c.825C>T had no influence on the humoral immune response. At month 1, CC genotype carriers had significantly increased T-cell responses compared to CT (
p
= 0.005) or TT (
p
= 0.02) genotypes. CC genotype carriers had an almost 6-fold increased probability compared to TT genotype carriers and an almost 3-fold increased probability compared to T-allele carriers to mount a SARS-CoV-2-specific T-cell response above the median value.
Conclusion:
CC genotype carriers of the
GNB3
c.825C>T polymorphism have an increased T-cell immune response to SARS-CoV-2, which may indicate better T-cell-mediated protection against COVID-19 after vaccination with mRNA-1273.
Summary Background The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, ...Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses. Methods We report data for a patient who was admitted to the Klinikum Schwabing (Munich, Germany) for severe acute respiratory infection. We did diagnostic RT-PCR and indirect immunofluorescence. From time of diagnosis, respiratory, faecal, and urine samples were obtained for virus quantification. We constructed a maximum likelihood tree of the five available complete MERS-CoV genomes. Findings A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klinikum Schwabing on March 19, 2013, on day 11 of illness. He had been diagnosed with multiple myeloma in 2008, and had received several lines of treatment. The patient died on day 18, due to septic shock. MERS-CoV was detected in two samples of bronchoalveolar fluid. Viral loads were highest in samples from the lower respiratory tract (up to 1·2 × 106 copies per mL). Maximum virus concentration in urine samples was 2691 RNA copies per mL on day 13; the virus was not present in the urine after renal failure on day 14. Stool samples obtained on days 12 and 16 contained the virus, with up to 1031 RNA copies per g (close to the lowest detection limit of the assay). One of two oronasal swabs obtained on day 16 were positive, but yielded little viral RNA (5370 copies per mL). No virus was detected in blood. The full virus genome was combined with four other available full genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation. The time of the common ancestor was halfway through 2011. Addition of novel genome data from an unlinked case treated 6 months previously in Essen, Germany, showed a clustering of viruses derived from Qatar and the United Arab Emirates. Interpretation We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches. Funding European Union; German Centre for Infection Research; German Research Council; and German Ministry for Education and Research.
Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction ...in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity. Here, using the Friend retrovirus mouse model, we show that following infection NK cells increase nutrient uptake, including amino acids and iron, and reprogram their metabolic machinery by increasing glycolysis and mitochondrial metabolism. Specific deletion of the amino acid transporter Slc7a5 has only discrete effects on NK cells, but iron deficiency profoundly impaires NK cell antiviral functions, leading to increased viral loads. Our study thus shows the requirement of nutrients and metabolism for the antiviral activity of NK cells, and has important implications for viral infections associated with altered iron levels such as HIV and SARS-CoV-2.
•The management of the SARS-Cov-2 pandemic in Germany was named a success story.•A statistically sound estimate of excess mortality has not been made for Germany.•The excess mortality during the ...first wave of the pandemic is 8071 cases.•After age adjustment, there were 4926 fewer deaths than expected.•Several factors explain the comparatively mild course of the pandemic in Germany.
The first wave of the SARS-CoV-2 pandemic in Germany lasted from week 10 to 23 in 2020. The aim is to provide estimates of excess mortality in Germany during this time.
We analyzed age-specific numbers of deaths per week from 2016 to week 26 in 2020. We used weekly mean numbers of deaths of 2016–2019 to estimate expected weekly numbers for 2020. We estimated standardized mortality ratios (SMR) and 95% confidence intervals.
During the first wave observed numbers of deaths were higher than expected for age groups 60–69, 80–89, and 90+. The age group 70–79 years did not show excess mortality. The net excess number of deaths for weeks 10–23 was +8,071. The overall SMR was 1•03 (95%CI 1•03–1•04). The largest increase occurred among people aged 80–89 and 90+ (SMR=1•08 and SMR=1•09). A sensitivity analysis that accounts for demographic changes revealed an overall SMR of 0•98 (95%CI 0•98–0•99) and a deficit of 4,926 deaths for week 10–23, 2020.
The excess mortality existed for two months. The favorable course of the first wave may be explained by a younger age at infection at the beginning of the pandemic, lower contact rates, and a more efficient pandemic management.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has a major impact on transplant recipients, with mortality rates up to 20%. Therefore, the effect of established messenger RNA ...(mRNA)-based SARS-CoV-2 vaccines have to be evaluated for solid organ transplant patients (SOT) since they are known to have poor responses after vaccination. We investigated the SARS-CoV-2 immune response via SARS-CoV-2 IgG detection in 23 renal transplant recipients after two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol. The antibody response was evaluated once with an anti-SARS-CoV-2 IgG CLIA 15.8 +/- 3.0 days after the second dose. As a control, SARS-CoV-2 IgG was determined in 23 healthcare workers (HCW) and compared to the patient cohort. Only 5 of 23 (22%) renal transplant recipients were tested positive for SARS-CoV-2 IgG antibodies after the second dose of vaccine. In contrast, all 23 (100%) HCWs were tested positive for antibodies after the second dose. Thus, the humoral response of renal transplant recipients after two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech, Kronach, Germany) is impaired and significantly lower compared to healthy controls (22% vs. 100%;
= 0.0001). Individual vaccination strategies might be beneficial in these vulnerable patients.
We investigated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a group of convalescent, potential blood donors in Germany who had PCR-confirmed SARS-CoV-2 ...infection. Sixty days after onset of symptoms, 13/78 (17%) study participants had borderline or negative results to an ELISA detecting IgG against the S1 protein of SARS-CoV-2. We analyzed participants with PCR-confirmed infection who had strong antibody responses (ratio >3) as positive controls and participants without symptoms of SARS-CoV-2 infection and without household contact with infected patients as negative controls. Using interferon-γ ELISpot, we observed that 78% of PCR-positive volunteers with undetectable antibodies showed T cell immunity against SARS-CoV-2. We observed a similar frequency (80%) of T-cell immunity in convalescent donors with strong antibody responses but did not detect immunity in negative controls. We concluded that, in convalescent patients with undetectable SARS-CoV-2 IgG, immunity may be mediated through T cells.
The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected ...people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are still urgently needed. Complementary medicine is used along with standard medical treatment and accessible to a vast majority of people worldwide. Natural products with antiviral activity may contribute to improve the overall condition of SARS-CoV-2 infected individuals. In the present study, we investigated the antiviral activity of glycyrrhizin, the primary active ingredient of the licorice root, against SARS-CoV-2. We demonstrated that glycyrrhizin potently inhibits SARS-CoV-2 replication in vitro. Furthermore, we uncovered the underlying mechanism and showed that glycyrrhizin blocks the viral replication by inhibiting the viral main protease M
that is essential for viral replication. Our data indicate that the consumption of glycyrrhizin-containing products such as licorice root tea of black licorice may be of great benefit for SARS-CoV-2 infected people. Furthermore, glycyrrhizin is a good candidate for further investigation for clinical use to treat COVID-19 patients.
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