Molecular mechanisms responsible for SARS-CoV-2 antibody waning and vaccine escape in Omicron sublineages BA.4 and BA.5.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome continue to threaten the global landscape of the coronavirus disease 2019 (COVID-19) pandemic. The Omicron variant (B.1.1.529) rapidly displaced previous 'variants of concern' (VoC) in 2021 due to its high rate of transmissibility and multitude of mutations. This global influx of infections saturated healthcare systems, overwhelmed testing capacity and case reporting, and increased the COVID-19 death toll. Global health leaders are now being faced with the most transmissible COVID-19 variants yet, the Omicron sublineages BA.4 and BA.5, which contain additional spike protein (S) mutations from previous Omicron and VoC serotypes. With universally observed antibody waning, increasing vaccine-variant mismatch, and resuming international travel, the stage is set for unprecedented levels of breakthrough infections and superspreading events. In this paper, we raise awareness to these novel variants and provide context for the high likelihood of an upcoming wave of infection capable of inflicting significant disease burden on a global scale.

Increased Presence of Antibodies against Type I Interferons and Human Endogenous Retrovirus W in Intensive Care Unit COVID-19 Patients.

In this work, we observed an increased presence of antibodies (Abs) against type I interferon (IFN-I) in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to non-ICU COVID-19 patients and healthy control (HC) subjects. Human endogenous retrovirus W (HERV-W) can reactivate after viral infection; therefore, we also investigated the presence of antibodies against HERV-W envelope (HERV-W-env)-derived epitopes. A total of 113 subjects (41 female and 72 male subjects) were analyzed. A significant difference in autoantibodies against IFN-α, IFN-ω, and HERV-W was observed between HCs and ICU patients; indeed, the latter have higher levels of autoantibodies against IFN-α, IFN-ω, and HERV-W than subjects with mild COVID-19 and HCs. Neutralizing anti-IFN-I autoantibodies may affect the ability of IFN-I to bind to the type I interferon receptor (IFNAR), blocking the activation of the antiviral response. IMPORTANCE In this work, we report the increased presence of IFN autoantibodies in correlation with HERV-W-env autoantibodies in ICU COVID-19 patients. The novelty of the results is in the association of these IFN autoantibodies with autoantibodies against HERV-W-env, a protein recently discovered to be overexpressed in lymphocytes of COVID-19 patients and correlated with severe disease and pneumonia. Type I IFNs are part of a complex cross-regulatory network; however, in a small percentage of cases, the increase in autoantibodies against these proteins may lead to damage to the host instead of protection against infectious diseases.

Genomic Snapshot of SARS-CoV-2 in Migrants Entering Through Mediterranean Sea Routes.

In December 2019, a novel coronavirus emerged in Wuhan, China, rapidly spreading into a global pandemic. Italy was the first European country to experience SARS-CoV-2 epidemic, and one of the most severely affected during the first wave of diffusion. In contrast to the general restriction of people movements in Europe, the number of migrants arriving at Italian borders via the Mediterranean Sea route in the summer of 2020 had increased dramatically, representing a possible, uncontrolled source for the introduction of novel SARS-CoV-2 variants. Importantly, most of the migrants came from African countries showing limited SARS-CoV-2 epidemiological surveillance. In this study, we characterized the SARS-CoV-2 genome isolated from an asymptomatic migrant arrived in Sardinia via the Mediterranean route in September 2020, in comparison with SARS-CoV-2 isolates arrived in Sicily through the Libyan migration route; with SARS-CoV-2 isolates circulating in Sardinia during 2020; and with viral genomes reported in African countries during the same summer. Results showed that our sequence is not phylogenetically related to isolates from migrants arriving in Sicily, nor to isolates circulating in Sardinia territory, having greater similarity to SARS-CoV-2 genomes reported in countries known for being sites of migrant embarkation to Italy. This is in line with the hypothesis that most SARS-CoV-2 infections among migrants have been acquired prior to embarking to Italy, possibly during the travel to or the stay in crowded Libyan immigrant camps. Overall, these observations underline the importance of dedicated SARS-CoV-2 surveillance of migrants arriving in Italy and in Europe through the Mediterranean routes.

Emerging Clinical Features of COVID-19 Related Pancreatitis: Case Reports and Review of the Literature.

INTRODUCTION: SARS-CoV-2 is fundamentally a respiratory pathogen with a wide spectrum of symptoms. The COVID-19 related pancreatitis is less considered than other clinical features. The purpose is to describe two cases of pancreatitis associated with COVID-19. METHODOLOGY: Patients' demographics, clinical features, laboratory, and instrumental findings were collected. RESULTS: Two patients admitted to the hospital were diagnosed with COVID-19 and severe acute pancreatitis, according to the Atlanta criteria. Other causes of acute pancreatitis were excluded. Treatment included broad-spectrum antibiotics, proton pump inhibitors, and low molecular weight heparin. Steroids, oxygen, antifungal treatment, and pain killers were administered when appropriate. Both patients were asymptomatic, with normal vital parameters and blood exams, and were discharged in a good condition. CONCLUSION: It is recommendable to include lipase and amylase on laboratory routine tests in order to evaluate the need for the abdominal CT-scan and specific therapy before hospital admission of the patients with COVID-19 related life-threatening acute pancreatitis.

COVID-19 imported cases and severity: expected information from genomic characterization of SARS-CoV-2 strains in Mozambique.

INTRODUCTION: The novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), etiological agent of coronavirus disease 2019 (COVID-19) was first reported in China in December 2019 and spread worldwide. As of March 6th, 2021, there have been 116,670,105 million confirmed cases globally including 2,592,085 deaths. COVID-19 cases have been reported in 219 countries and territories, creating global panic. Mozambique has witnessed the evolution of COVID-19 epidemic associated with the weakness of health system, mostly in terms of laboratory diagnosis capacity, concerns on compliance to effective public health measures including physical distancing, use of masks in crowded indoor areas, hand hygiene, isolation and quarantine of people. METHODOLOGY: The data included in this study were collected from published articles regarding COVID-19 imported cases and severity in Africa, especially in Mozambique. Additionally, official documents of COVID-19 epidemiology from Minister of Health and National Institute of Health of Mozambique from 22nd of March 2020 to 1st of August 2020 were included. RESULTS: The SARS-CoV-2 strains imported mainly from South Africa and European countries might have been playing an important role on COVID-19 epidemic evolution in Mozambique. CONCLUSIONS: These circulating strains in the country, might be similar enough to the strains found in other countries, yet the genomic characterization is needed particularly during the phase of borders reopening through understanding the source of infections and guiding the implementation of containment and mitigation measures in the country.

"Swab Team" in the SARS-CoV-2 outbreak containment among healthcare workers.

INTRODUCTION: To analyze the virus spread among Sassari Hospital staff in the first Covid-19 wave and the impact of the Swab Team, a multidisciplinary task force entitled of nasopharyngeal swab collection and testing. METHODOLOGY: Nasopharyngeal swabs from HCWs between March 6 and May 28 2020 are evaluated. RESULTS: 4919 SARS-CoV-2 tests were performed on 3521 operators. Nurses and doctors are the categories at highest risk. After the Swab Team institution, the average number of swabs raised from 47/day to 86/day (p = 0.007). Positive samples decreased from 18.6% to 1.7% (p < 0.0001). CONCLUSIONS: The Swab Team is effective in increasing the cases tested and in reducing the reporting time. Procedure standardization reduces the risk for all the subjects involved (no transmission among swab team members, nor during the sample collection).

Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study.

BACKGROUND: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. METHODS: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. FINDINGS: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

A straightforward molecular strategy to retrospectively investigate the spread of SARS-CoV-2 VOC202012/01 B.1.1.7 variant.

The spread of new SARS-CoV-2 variants represents a serious threat worldwide, thus rapid and cost-effective methods are required for their identification. Since November 2020, the TaqPath COVID-19 assay (Thermo Fisher Scientific) has been used to identify viral strains of the new lineage B.1.1.7, since it fails to detect the S-gene with the ∆69/70 deletion. Here, we proposed S-gene mutations screening with the Allplex SARS-CoV-2 assay (Seegene), another widely used RT-PCR test that targets Sarbecovirus E, SARS-CoV-2 N, and RdRp/S genes. Accordingly, we evaluated the S gene amplification curve pattern compared to those of the other genes. Exploiting an Allplex assay-generated dataset, we screened 663 RT-PCR digital records, including all SARS-CoV-2 respiratory samples tested in our laboratory with the Allplex assay between January 1st and February 25th, 2021. This approach enabled us to detect 64 samples with peculiar non-sigmoidal amplification curves. Sequencing a selected group of 4 RNA viral genomes demonstrated that those curves were associated with B.1.1.7 variant strains. Our results strongly suggest that B.1.1.7 variant spread has begun in this area at least since January and imply the potential of these analytical methods to track and characterize the spread of B.1.1.7 strains in those areas where Allplex SARS-CoV-2 datasets have been previously recorded.

HCoV-NL63 and SARS-CoV-2 Share Recognized Epitopes by the Humoral Response in Sera of People Collected Pre- and during CoV-2 Pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause serious illness in older adults and people with chronic underlying medical conditions; however, children and young people are often asymptomatic or with mild symptoms. We evaluated the presence of specific antibodies (Abs) response against Human coronavirus NL63 (HCoV-NL63) S protein epitopes (NL63-RBM1, NL63-RBM2_1, NL63-RBM2_2, NL63-RBM3, NL63-SPIKE541-554, and NL63-DISC-like) and SARS-CoV-2 epitopes (COV2-SPIKE421-434 and COV2-SPIKE742-759) in plasma samples of pre-pandemic, mid-pandemic, and COVID-19 cohorts by indirect ELISA. Moreover, a competitive assay was performed to check for cross reactivity response between COV2-SPIKE421-434 and NL63-RBM3 among patients with a definitive diagnosis of SARS-CoV-2. Immune reaction against all SARS-CoV-2 and HCoV-NL63 epitopes showed a significantly higher response in pre-pandemic patients compared to mid-pandemic patients. The results indicate that probably antibodies against HCoV-NL63 may be able to cross react with SARS-CoV-2 epitopes and the higher incidence in pre-pandemic was probably due to the timing of collection when a high incidence of HCoV-NL63 is reported. In addition, the competitive assay showed cross-reactivity between antibodies directed against COV2-SPIKE421-434 and NL63-RBM3 peptides. Pre-existing HCoV-NL63 antibody response cross reacting with SARS-CoV-2 has been detected in both pre- and mid-pandemic individual, suggesting that previous exposure to HCoV-NL63 epitopes may produce antibodies which could confer a protective immunity against SARS-CoV-2 and probably reduce the severity of the disease.

A challenging complication following SARS-CoV-2 infection: a case of pulmonary mucormycosis.

Severe acute respiratory syndrome coronavirus 2 infection might induce a significant and sustained lymphopenia, increasing the risk of developing opportunistic infections. Mucormycosis is a rare but severe invasive fungal infection, mainly described in immunocompromised patients. The first case of a patient diagnosed with coronavirus disease (COVID-19) who developed a pulmonary mucormycosis with extensive cavitary lesions is here reported. This case highlights how this new coronavirus might impair the immune response, exposing patients to higher risk of developing opportunistic infections and leading to worse outcomes.

Air pollution and other risk factors might buffer COVID-19 severity in Mozambique.

Mozambique is located on the East Coast of Africa and was one of the last countries affected by COVID-19. The first case was reported on 22 March 2020 and since then the cases have increased gradually as they have in other countries worldwide. Environmental and population characteristics have been analyzed worldwide to understand their possible association with COVID-19. This article seeks to highlight the evolution and the possible contribution of risk factors for COVID-19 severity according to the available data in Mozambique. The available data highlight that COVID-19 severity can be magnified mainly by hypertension, obesity, cancer, asthma, HIV/SIDA and malnutrition conditions, and buffered by age (youthful population). Due to COVID-19 epidemic evolution, particularly in Cabo Delgado, there is the need to increase laboratory diagnosis capacity and monitor compliance of preventive measures. Particular attention should be given to Cabo Delgado, including its isolation from other provinces, to overcome local transmission and the spread of SARS-CoV-2.

Inappropriate Nasopharyngeal Sampling for SARS-CoV-2 Detection Is a Relevant Cause of False-Negative Reports.

Reverse transcriptase polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 mRNA on nasopharyngeal swab is the standard for diagnosing active COVID-19 disease in asymptomatic cases and in symptomatic patients without the typical radiologic findings. For the present COVID-19 outbreak in Italy, we describe 4 symptomatic patients with negative RT-PCR results at the first nasopharyngeal swab, which became positive when collected a few hours later by an otolaryngologist. All the patients showed nasal obstruction. The present report suggests that inadequate nasopharyngeal sampling performed by untrained operators in the presence of nasal obstruction can be a relevant case of false-negative findings at RT-PCR, with a clear negative impact on the efforts to contain the current outbreak.

As COVID-19 cases, deaths and fatality rates surge in Italy, underlying causes require investigation.

COVID-19 case fatalities surged during the month of March 2020 in Italy, reaching over 10,000 by 28 March 2020. This number exceeds the number of fatalities in China (3,301) recorded from January to March, even though the number of diagnosed cases was similar (85,000 Italy vs. 80,000 China). Case Fatality Rates (CFR) could be somewhat unreliable because the estimation of total case numbers is limited by several factors, including insufficient testing and limitations in test kits and materials, such as NP swabs and PPE for testers. Sero prevalence of SARS-CoV-2 antibodies may help in more accurate estimations of the total number of cases. Nevertheless, the disparity in the differences in the total number of fatalities between Italy and China suggests investigation into several factors, such as demographics, sociological interactions, availability of medical equipment (ICU beds and PPE), variants in immune proteins (e.g., HLA, IFNs), past immunity to related CoVs, and mutations in SARS-CoV-2, could impact survival of severe COVID-19 illness survival and the number of case fatalities.

The novel zoonotic COVID-19 pandemic: An expected global health concern.

18 years ago, in 2002, the world was astonished by the appearance of Severe Acute Respiratory Syndrome (SARS), supported by a zoonotic coronavirus, called SARS-CoV, from the Guangdong Province of southern China. After about 10 years, in 2012, another similar coronavirus triggered the Middle East Respiratory Syndrome (MERS-CoV) in Saudi Arabia. Both caused severe pneumonia killing 774 and 858 people with 8700 cases of confirmed infection for the former, and 2494 for the latter, causing significant economic losses. 8 years later, despite the MERS outbreak remaining in certain parts of the world, at the end of 2019, a new zoonotic coronavirus (SARS-CoV-2) and responsible of coronavirus Disease (COVID-19), arose from Wuhan, Hubei Province, China. It spread rapidly and to date has killed 3,242 persons with more than 81,000 cases of infection in China and causing over 126,000 global cases and 5,414 deaths in 166 other countries around the world, especially Italy. SARS-CoV-2 would seem to have come from a bat, but the intermediate reservoir continues to be unknown. Nonetheless, as for SARS-CoV and MERS CoV, the Spillover effect linked to animal-human promiscuity, human activities including deforestation, illegal bush-trafficking and bushmeat, cannot be excluded. Recently, however, evidence of inter-human only transmission of SARS-CoV-2 has been accumulated and thus, the outbreak seems to be spreading by human-to-human transmission throughout a large part of the world. Herein we will provide with an update on the main features of COVID-19 and suggest possible solutions how to halt the expansion of this novel pandemic.

Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China.

As of 28 February 2020, Italy had 888 cases of SARS-CoV-2 infections, with most cases in Northern Italy in the Lombardia and Veneto regions. Travel-related cases were the main source of COVID-19 cases during the early stages of the current epidemic in Italy. The month of February, however, has been dominated by two large clusters of outbreaks in Northern Italy, south of Milan, with mainly local transmission the source of infections. Contact tracing has failed to identify patient zero in one of the outbreaks. As of 28 February 2020, twenty-one cases of COVID-19 have died. Comparison between case fatality rates in China and Italy are identical at 2.3. Additionally, deaths are similar in both countries with fatalities in mostly the elderly with known comorbidities. It will be important to develop point-of-care devices to aid clinicians in stratifying elderly patients as early as possible to determine the potential level of care they will require to improve their chances of survival from COVID-19 disease.

2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness.

On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.