Prior SARS-CoV-2 infection and COVID-19 vaccine effectiveness against outpatient illness during widespread circulation of SARS-CoV-2 Omicron variant, US Flu VE network.

BACKGROUND: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). METHODS: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. RESULTS: Four hundred fifty-five (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%-99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%-76%) against Omicron; VE against Delta could not be estimated. CONCLUSIONS: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants.

Severe COVID-19 Myocarditis in a Young Unvaccinated Patient.

Coronavirus disease 2019 (COVID-19) myocarditis is a rare but serious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been associated with high-case fatality. For a very long time, since the beginning of the pandemic, there were no definitive guidelines to diagnose and manage this condition, probably secondary to the gaps in understanding the exact pathophysiology of the disease. We present the case of a young, unvaccinated female, with no comorbidities, who had an aggressively progressive COVID-19 myocarditis that was fatal. The patient presented with exertional dyspnea of two days duration and was found to be tachycardic with a heart rate ranging between 130-150 beats per minute. A nasopharyngeal swab for SARS CoV-2 was positive and a bedside echocardiogram showed a low ejection fraction of 20%. Within hours of presenting, she experienced a rapid decompensation requiring intubation. Due to fulminant myocarditis with cardiogenic shock, the patient was planned for cardiac catheterization, Impella placement, and extracorporeal membrane oxygenation (ECMO) support. The cardiac catheterization revealed non-obstructive coronary arteries and the hemodynamics suggested biventricular failure. However, around the time of the cardiac catheterization procedure, she had two events of cardiac arrest with pulseless electrical activity and unfortunately could not be revived after the second arrest despite all resuscitative efforts.

Retrospective Observational Study of Complete Blood Count (CBC) Parameters and ICU Mortality of COVID-19 Disease in Delta Variant and Omicron Variant in a Community-Based Hospital in New York City.

BACKGROUND: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the official name of COVID-19, a respiratory infection that had the first case reported from the Hubei province of China on December 8, 2019. This virus is the main etiological agent behind the most dreaded pandemic of pneumonia that has spread to the entire world in a brief period and continues to pose a threat. The first wave corresponded with the period from February 2020 to June 2020, the Delta variant occurred around the middle of June 2021 and the Omicron wave was reported from December 2021 to February 2022. Objective: This study aims to compare the Delta and the Omicron variants of COVID-19 infection in a community-based hospital in New York City considering the comparison of ICU admissions in both variants. We aim to study the comparison of complete blood count (CBC) parameters and inflammatory markers of patients admitted to ICU stratified by two waves of COVID-19 infection. We aim to analyze the association of CBC parameters at admission and the discharge during ICU stay in both variants. We also aim to study the association of CBC parameters at admission and discharge with ICU mortality in both variants. METHODS: We conducted a retrospective observational study based on data from randomly selected hospitalized patients with COVID-19 in a community-based hospital in New York City during the Delta variant and the Omicron wave. A total of 211 patients COVID-19 positive from June to July 2021 (Delta variant) and 148 patients from December to February 2022 (Omicron wave) were included in the study. A comparison was done between the basic characteristics of patients with and without ICU admissions in both variants of COVID-19. We compared the relationship of different parameters of CBC (hemoglobin (Hgb), white blood count (WBC), lymphocytes, neutrophils, and platelets) on ICU admission and further analyzed any changes associated with ICU mortality. Logistic regression was performed to evaluate the relationship of different presenting CBCs on patients' disposition to ICU.  Result: A total of 211 patients (106 female) in the Delta wave (2021 variant) and 148 patients (80 female) in the Omicron wave (2022 variant) with an average ages of 60.9 ±18.10 (Delta variant) and 63.2 ± 19.10 (Omicron variant) were included in this study. There were 45 patients (21.3%) in the Delta wave and 42 patients (28.4%) in the Omicron wave were admitted to ICU. The average length of hospital stay was seven days in the Delta wave and nine days in the Omicron wave. No significant association was found between presenting cell count and ICU admission (p>0.05). Significant associations were found between different cell counts on admission and discharge and death in Delta waves except Hgb and platelets on admission. However, in the Omicron variant, a significant association was found only between WBC on admission and discharge, and Hgb and neutrophil on discharge with death in the univariate model. CONCLUSION:  Comparative study of different clinical parameters between the Delta and the Omicron variants of COVID-19 with the correlation of ICU stay and mortality can be used as a beneficial modality in assessing the outcome of the disease.

False-Positive Human Immunodeficiency Virus Results in COVID-19 Patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, which causes coronavirus disease 2019 (COVID-19) disease, was first described in 2019 and became a pandemic in 2020. Although it is possible for two viruses to co-infect together, a rarer phenomenon of false-positive results due to cross-reactivity between viruses is also possible. Herein, we present two cases of the false-positive human immunodeficiency virus (HIV) results in those infected with COVID-19. Both patients were screened for HIV and were initially found to be positive with the fourth-generation test. A subsequent blood test revealed no viral load, and an enzyme-linked immunosorbent assays (ELISA) test indicated no reactivity to HIV, thus the false initial screening test. SARS-CoV-2 is an enveloped RNA virus with its outer surface containing a spike-like glycoprotein, which allows it to recognize host cells and invade. HIV-1 gp41 and SARS-CoV-2 share several structural sequences and motifs. These similarities could explain cross-reactivity and false-positive results when screening for HIV in the presence of COVID. The presence of HIV must be confirmed through more specific laboratory tests such as ELISA.

Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro.

SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro). Polyprotein processing is essential yet incompletely understood. We studied Mpro-mediated processing of the nsp7-11 polyprotein, whose mature products include cofactors of the viral replicase, and identified the order of cleavages. Integrative modeling based on mass spectrometry (including hydrogen-deuterium exchange and cross-linking) and x-ray scattering yielded a nsp7-11 structural ensemble, demonstrating shared secondary structural elements with individual nsps. The pattern of cross-links and HDX footprint of the C145A Mpro and nsp7-11 complex demonstrate preferential binding of the enzyme active site to the polyprotein junction sites and additional transient contacts to help orient the enzyme on its substrate for cleavage. Last, proteolysis assays were used to characterize the effect of inhibitors/binders on Mpro processing/inhibition using the nsp7-11 polyprotein as substrate.

Understanding of COVID-19 vaccination in pregnant female - Hesitancy and acceptance: A prospective observational study

Background: India is one of the most severely affected countries due to the COVID-19 pandemic. A higher risk of severe illness and complications from COVID-19 had been observed in pregnant women as compared to nonpregnant women. The government of India on July 2, 2021, provided approval for the vaccination of pregnant women against COVID-19. A little data regarding the safety or harm during pregnancy of vaccination were available that time. Lack of safety data, fear, mistrust, underestimation of efficacy of vaccine, and chaos due to pandemic makes indecisive surrounding for pregnant women and this causes hesitancy with decision making about the COVID-19 vaccination. Aims and Objectives: This study aims to analyze the willingness and hesitancy of pregnant women to get vaccinated against COVID-19. Materials and Methods: This prospective study was conducted in a tertiary care institute in Northern India. Five hundred antenatal women who were eligible for COVID-19 vaccination were included in this study. Informed consent has been taken and data were analyzed after filling face to face questionnaire regarding vaccine acceptance or hesitancy. Results: The present study revealed low acceptance of COVID-19 vaccination in pregnancy. Prime reasons for the same are no allowance by the family and the possibility of vaccine harming the baby. Conclusion: Specific efforts should be directed toward high-risk populations including pregnant women and those who are planning for pregnancy. This will promote vaccination rates by increasing people's trust in immunization and the health-care system. [ FROM AUTHOR]

Observational Study of Thrombotic Events in a Random Cohort of Hospitalized COVID-19 Patients at a Community-Based Hospital of New York City During the Beginning of the 2020 Pandemic.

Coronavirus disease 2019 (COVID-19) continues to pose an unprecedented challenge for the entire world and the healthcare system. Different theories have been proposed elucidating the pathophysiological mechanisms attributing to high mortality and morbidity in COVID-19 infection. Out of them, thrombosis and procoagulant state have managed to earn the maximum limelight. We conducted an observational study based on data from randomly selected 349 hospitalized patients with COVID-19 infection in a community-based hospital in New York City during the first wave of the COVID-19 viral surge in March 2020. The main objective of our study was to assess the risk and occurrence of thrombotic events (both venous and arterial) among the hospitalized patients including the intensive care unit (ICU) and non-ICU admissions with confirmed COVID-19 infection. The primary outcome in our study was defined as the thrombotic events that included myocardial infarction (MI), deep venous thrombosis (DVT), cerebrovascular accidents (CVA), and pulmonary embolism (PE). The study correlated the association of thrombotic events with the level of biomarkers of interest: D-dimer >1000 ng/ml, troponin-I >1 ng/ml, or both. The association of D-dimers and troponin-I with thrombotic events was measured using both univariate and multivariate Cox proportional hazard (PH) regression analysis. Out of a total of 349 patients, 78 patients (22.35%) were found to have elevated biomarkers (D-dimer >1000 ng/ml and/or troponin-I >1 ng/ml) and were categorized as a high-risk group. Eighty-nine patients developed thrombotic complications (evidence of more than one thrombotic event was found in several patients). Two-hundred seventy-one (77.65%) patients had no documentation of thrombosis. The incidence of thrombotic events included myocardial infarction (MI; N=45; 12.8%), cerebrovascular accidents (CVA; N=16; 4.5%), deep venous thrombosis (DVT; N=16; 4.5%), and pulmonary embolism (PE; N=9; 2.57%).

Emergence and expansion of highly infectious spike protein D614G mutant SARS-CoV-2 in central India.

COVID-19 has emerged as global pandemic with largest damage to the public health, economy and human psyche.The genome sequence data obtained during the ongoing pandemic are valuable to understand the virus evolutionary patterns and spread across the globe. Increased availability of genome information of circulating SARS-CoV-2 strains in India will enable the scientific community to understand the emergence of new variants and their impact on human health. The first case of COVID-19 was detected in Chambal region of Madhya Pradesh state in mid of March 2020 followed by multiple introduction events and expansion of cases within next three months. More than 5000 COVID-19 suspected samples referred to Defence Research and Development Establishment, Gwalior, Madhya Pradesh were analyzed during the nation -wide lockdown and unlock period. A total of 136 cases were found positive over a span of three months that included virus introduction to the region and its further spread. Whole genome sequences employing Oxford nanopore technology were generated for 26 SARS-CoV-2 circulating in 10 different districts in Madhya Pradesh state of India. This period witnessed index cases with multiple travel histories responsible for introduction of COVID-19 followed by remarkable expansion of virus. The genome wide substitutions including in important viral proteins were identified. The detailed phylogenetic analysis revealed the circulating SARS-CoV-2 clustered in multiple clades including A2a, A4 and B. The cluster-wise segregation was observed, suggesting multiple introduction links and subsequent evolution of virus in the region. This is the first comprehensive whole genome sequence analysis from central India, which revealed the emergence and evolution of SARS-CoV-2 during thenation-wide lockdown and unlock.

Revealing the Structural Plasticity of SARS-CoV-2 nsp7 and nsp8 Using Structural Proteomics.

Coronavirus (CoV) nonstructural proteins (nsps) assemble to form the replication-transcription complex (RTC) responsible for viral RNA synthesis. nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA-dependent RNA polymerase and other nsps. To date, no structure of the full-length SARS-CoV-2 nsp7:nsp8 complex has been published. The current understanding of this complex is based on structures from truncated constructs, with missing electron densities, or from related CoV species where SARS-CoV-2 nsp7 and nsp8 share upward of 90% sequence identity. Despite available structures solved using crystallography and cryo-EM representing detailed static snapshots of the nsp7:nsp8 complex, it is evident that the complex has a high degree of structural plasticity. However, relatively little is known about the conformational dynamics of the individual proteins and how they complex to interact with other nsps. Here, the solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and cross-linking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7 and nsp8 proteins and the nsp7:nsp8 protein complex. Results presented from the two techniques are complementary and validate the interaction surfaces identified from the published three-dimensional heterotetrameric crystal structure of the SARS-CoV-2 truncated nsp7:nsp8 complex. Furthermore, mapping of XL-MS data onto higher-order complexes suggests that SARS-CoV-2 nsp7 and nsp8 do not assemble into a hexadecameric structure as implied by the SARS-CoV full-length nsp7:nsp8 crystal structure. Instead, our results suggest that the nsp7:nsp8 heterotetramer can dissociate into a stable dimeric unit that might bind to nsp12 in the RTC without significantly altering nsp7-nsp8 interactions.

Pulmonary Pathology of COVID-19 Following 8 Weeks to 4 Months of Severe Disease: A Report of Three Cases, Including One With Bilateral Lung Transplantation.

OBJECTIVES: Current knowledge of the pulmonary pathology of coronavirus disease 2019 (COVID-19) is based largely on postmortem studies. In most, the interval between disease onset and death is relatively short (<1 month). Information regarding lung pathology in patients who survive for longer periods is scant. We describe the pathology in three patients with severe COVID-19 who underwent antemortem examination of lung tissue at least 8 weeks after initial diagnosis. METHODS: We conducted a retrospective case series. RESULTS: The first patient developed acute respiratory failure and was started on extracorporeal membrane oxygenation (ECMO) on day 21, with subsequent hemothorax. Debridement (day 38) showed extensive lung infarction with diffuse alveolar damage and Candida overgrowth. The second patient developed acute respiratory failure requiring mechanical ventilation that did not improve despite ECMO. Surgical lung biopsy on day 74 showed diffuse interstitial fibrosis with focal microscopic honeycomb change. The third patient also required ECMO and underwent bilateral lung transplantation on day 126. The explanted lungs showed diffuse interstitial fibrosis with focal microscopic honeycomb change. CONCLUSIONS: This series provides histologic confirmation that complications of COVID-19 after 8 weeks to 4 months of severe disease include lung infarction and diffuse interstitial fibrosis.

Thoracic imaging in COVID-19.

The typical findings of COVID-19 on chest radiography and computed tomography (CT) include bilateral, multifocal parenchymal opacities (ground-glass opacities with or without consolidation, and "crazy paving"). In most cases, the opacities are predominantly in the peripheral and lower lung zones, and several have rounded morphology. However, these imaging findings are not pathognomonic for COVID-19 pneumonia and can be seen in other viral and bacterial infections, as well as with noninfectious causes such as drug toxicity and connective tissue disease. Most radiology professional organizations and societies recommend against routine screening CT to diagnose or exclude COVID-19.