mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine.

Background: The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination. Objective: However, the impact of these new vaccine formats with unclear effects on the long-term Ab response - including isotype, subclass, and their type of Fc glycosylation - is less explored. Methods: Here, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270. Results: We show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses - the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations. Conclusion: In summary, the study suggests a comparable "adjuvant" potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described TH1-driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy.

mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine

Background The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination. Objective However, the impact of these new vaccine formats with unclear effects on the long-term Ab response – including isotype, subclass, and their type of Fc glycosylation – is less explored. Methods Here, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270. Results We show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses – the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations. Conclusion In summary, the study suggests a comparable "adjuvant” potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described TH1-driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy.

A Rare Case of Lupus Transverse Myelitis in a Post-COVID-19 Patient Steven Gitarts

Case Diagnosis: Lupus patient develops transverse myelitis status post COVID-19 infection Case Description: A 24-year-old female with history of lupus, GERD, COVID (one year prior), presented with bilateral lower extremity weakness for one day, "penguin walking", paresthesia below the waist, fever, chills, and diarrhea. Setting(s): Acute Rehabilitation, Community Hospital - Brooklyn, NY Assessment/Results: Initially, patient's temperature was 102.7F. Sensation was intact, strength was decreased in right more than left lower extremity. Labs were positive for ANA, dsDNA, Smith, and RNP antibodies. Lumbar puncture showed elevated WBC, neutrophilia, increased IgG, and elevated protein: albumin ratio. MRI demonstrated ill-defined spinal cord areas of signal alteration at T2, T4, and T10-11 suggestive of transverse myelitis/lupus myelitis. Symptoms improved after steroids, and cyclophosphamide drip. During her rehabilitation course, lower extremity strength, ambulation, and endurance returned to baseline. Daily plaquenil and prednisone continued as well as outpatient cyclophosphamide monthly for 4 months. Discussion(s): Systemic lupus erythematosus (SLE), is rarely associated with transverse myelitis (TM). It occurs in 1-2% of patients within the first 5 years of SLE and reoccurs in 18-50%. Often, TM involves 3 or more contiguous spinal levels. The pathophysiology of TM in lupus is believed to be caused by thrombosis of the small vasculature supplying the thoracic spinal cord. Post-COVID hypercoagulable states could increase the risk. Motor involvement is usually bilateral, with spastic paraparesis being the most common. T5 to T8 are most frequently affected. T2 MRI signal intensity with spinal cord swelling, in the cervical or thoracic regions, is the gold standard test to confirm TM. A combination of methylprednisolone and cyclophosphamide is recommended. Conclusion(s): Transverse myelitis should be considered in lupus patients presenting with fever and a new or recurrent neurologic deficit. Radiologic findings present contiguously in the thoracic spinal cord and are less commonly discontiguous as in our patient. Early diagnosis and treatment are essential to achieve the best outcome.

Telehealth and Public Health Practice in the United States-Before, During, and After the COVID-19 Pandemic.

Telehealth is the use of electronic information and telecommunication technologies to provide care when the patient and the provider are not in the same room at the same time. Telehealth accounted for less than 1% of all Medicare Fee-for-Service outpatient visits in the United States in 2019 but grew to account for 46% of all visits in April 2020. Changes in reimbursement and licensure policies during the COVID-19 pandemic appeared to greatly facilitate this increased use. Telehealth will continue to account for a substantial portion of care provided in the United States and globally. A better understanding of telehealth approaches and their evidence base by public health practitioners may help improve their ability to collaborate with health care organizations to improve population health. The article summarizes the Centers for Disease Control and Prevention's (CDC's) approach to understanding the evidence base for telehealth in public health practice, possible applications for telehealth in public health practice, and CDC's use of telehealth to improve population health.

Telehealth Expansion During the COVID-19 Pandemic and Beyond.

Information and resources for health care providers.

Emergency Department and Intensive Care Unit Overcrowding and Ventilator Shortages in US Hospitals During the COVID-19 Pandemic, 2020-2021.

OBJECTIVE: In 2020, the COVID-19 pandemic overburdened the US health care system because of extended and unprecedented patient surges and supply shortages in hospitals. We investigated the extent to which several US hospitals experienced emergency department (ED) and intensive care unit (ICU) overcrowding and ventilator shortages during the COVID-19 pandemic. METHODS: We analyzed Health Pulse data to assess the extent to which US hospitals reported alerts when experiencing ED overcrowding, ICU overcrowding, and ventilator shortages from March 7, 2020, through April 30, 2021. RESULTS: Of 625 participating hospitals in 29 states, 393 (63%) reported at least 1 hospital alert during the study period: 246 (63%) reported ED overcrowding, 239 (61%) reported ICU overcrowding, and 48 (12%) reported ventilator shortages. The number of alerts for overcrowding in EDs and ICUs increased as the number of COVID-19 cases surged. CONCLUSIONS: Timely assessment and communication about critical factors such as ED and ICU overcrowding and ventilator shortages during public health emergencies can guide public health response efforts in supporting federal, state, and local public health agencies.

Real-Time CDC Consultation during the COVID-19 Pandemic-United States, March-July, 2020.

CONTEXT: In response to the COVID-19 pandemic, the Centers for Disease Prevention and Control (CDC) clinicians provided real-time telephone consultation to healthcare providers, public health practitioners, and health department personnel. OBJECTIVE: To describe the demographic and public health characteristics of inquiries, trends, and correlation of inquiries with national COVID-19 case reports. We summarize the results of real-time CDC clinician consultation service provided during 11 March to 31 July 2020 to understand the impact and utility of this service by CDC for the COVID-19 pandemic emergency response and for future outbreak responses. DESIGN: Clinicians documented inquiries received including information about the call source, population for which guidance was sought, and a detailed description of the inquiry and resolution. Descriptive analyses were conducted, with a focus on characteristics of callers as well as public health and clinical content of inquiries. SETTING: Real-time telephone consultations with CDC Clinicians in Atlanta, GA. PARTICIPANTS: Health care providers and public health professionals who called CDC with COVID-19 related inquiries from throughout the United States. MAIN OUTCOME MEASURES: Characteristics of inquiries including topic of inquiry, inquiry population, resolution, and demographic information. RESULTS: A total of 3154 COVID-19 related telephone inquiries were answered in real-time. More than half (62.0%) of inquiries came from frontline healthcare providers and clinical sites, followed by 14.1% from state and local health departments. The majority of inquiries focused on issues involving healthcare workers (27.7%) and interpretation or application of CDC's COVID-19 guidance (44%). CONCLUSION: The COVID-19 pandemic resulted in a substantial number of inquiries to CDC, with the large majority originating from the frontline clinical and public health workforce. Analysis of inquiries suggests that the ongoing focus on refining COVID-19 guidance documents is warranted, which facilitates bidirectional feedback between the public, medical professionals, and public health authorities.

The BioNTech / Pfizer vaccine BNT162b2 induces class-switched SARS-CoV-2-specific plasma cells and potential memory B cells as well as IgG and IgA serum and IgG saliva antibodies upon the first immunization (preprint)

To treat the SARS-CoV-2 virus, that enters the body through the respiratory tract, different vaccines in particular against the SARS-CoV-2 spike (S)-protein have been developed or are in the development process. For the BioNTech / Pfizer mRNA vaccine BNT162b2, which is injected twice, protection against COVID-19 has been described for the first weeks after the second vaccination. The underlying mechanisms of defense and the long-term effectiveness of this vaccine against COVID-19 are currently under investigation. In addition to the induction of systemic antibodies (Abs), Ab responses in the respiratory tract would help to form a first line of defense against SARS-CoV-2. Furthermore, protection depends on Fab-part-dependent neutralizing capacities, however, Fc-part-mediated effector mechanisms might also be important. Long-term defense would be based on the induction of long-lived antibody-producing plasma cells (PCs) and memory B cells. Here, we established different assays to analyze anti-SARS-CoV-2-S IgG and IgA Abs in blood serum and saliva as well as SARS-CoV-2-S1-reactive IgG and IgA PCs and potential memory B cells in the blood of individuals upon their first immunization with BNT162b2. We show that the vaccine induces in particular anti-SARS-CoV-2-S IgG1 and IgG3 as well as IgA1 and in some individuals also IgG2 and IgA2 serum Abs. In the saliva, we found no anti-SARS-CoV-2-S IgA, but instead IgG Abs. Furthermore, we found SARS-CoV-2-S reactive IgG+ blood PCs and potential memory B cells as well as SARS-CoV-2-S reactive IgA+ PCs and/or potential memory B cells in some individuals. Our data suggest that the vaccine induces a promising CD4+ T cell-dependent systemic IgG1 and IgG3 Ab response with IgG+ PCs and potential memory B cells. In addition to the systemic IgG response, the systemic IgA and saliva IgG response might help to improve a first line of defense in the respiratory tract against SARS-CoV-2 and its mutants.

Trends in Use of Telehealth Among Health Centers During the COVID-19 Pandemic - United States, June 26-November 6, 2020.

Telehealth can facilitate access to care, reduce risk for transmission of SARS-CoV-2 (the virus that causes coronavirus disease 2019 [COVID-19]), conserve scarce medical supplies, and reduce strain on health care capacity and facilities while supporting continuity of care. Health Resources and Services Administration (HRSA)-funded health centers* expanded telehealth† services during the COVID-19 pandemic (1). The Centers for Medicare & Medicaid Services eliminated geographic restrictions and enhanced reimbursement so that telehealth services-enabled health centers could expand telehealth services and continue providing care during the pandemic (2,3). CDC and HRSA analyzed data from 245 health centers that completed a voluntary weekly HRSA Health Center COVID-19 Survey§ for 20 consecutive weeks to describe trends in telehealth use. During the weeks ending June 26-November 6, 2020, the overall percentage of weekly health care visits conducted via telehealth (telehealth visits) decreased by 25%, from 35.8% during the week ending June 26 to 26.9% for the week ending November 6, averaging 30.2% over the study period. Weekly telehealth visits declined when COVID-19 cases were decreasing and plateaued as cases were increasing. Health centers in the South and in rural areas consistently reported the lowest average percentage of weekly telehealth visits over the 20 weeks, compared with health centers in other regions and urban areas. As the COVID-19 pandemic continues, maintaining and expanding telehealth services will be critical to ensuring access to care while limiting exposure to SARS-CoV-2.

Telehealth Practice Among Health Centers During the COVID-19 Pandemic - United States, July 11-17, 2020.

Early in the coronavirus disease 2019 (COVID-19) pandemic, in-person ambulatory health care visits declined by 60% across the United States, while telehealth* visits increased, accounting for up to 30% of total care provided in some locations (1,2). In March 2020, the Centers for Medicare & Medicaid Services (CMS) released updated regulations and guidance changing telehealth provisions during the COVID-19 Public Health Emergency, including the elimination of geographic barriers and enhanced reimbursement for telehealth services† (3-6). The Health Resources and Services Administration (HRSA) administers a voluntary weekly Health Center COVID-19 Survey§ to track health centers' COVID-19 testing capacity and the impact of COVID-19 on operations, patients, and staff. CDC and HRSA analyzed data from the weekly COVID-19 survey completed by 1,009 HRSA-funded health centers (health centers¶) for the week of July 11-17, 2020, to describe telehealth service use in the United States by U.S. Census region,** urbanicity,†† staffing capacity, change in visit volume, and personal protective equipment (PPE) supply. Among the 1,009 health center respondents, 963 (95.4%) reported providing telehealth services. Health centers in urban areas were more likely to provide >30% of health care visits virtually (i.e., via telehealth) than were health centers in rural areas. Telehealth is a promising approach to promoting access to care and can facilitate public health mitigation strategies and help prevent transmission of SARS-CoV-2 and other respiratory illnesses, while supporting continuity of care. Although CMS's change of its telehealth provisions enabled health centers to expand telehealth by aligning guidance and leveraging federal resources, sustaining expanded use of telehealth services might require additional policies and resources.