Transient Immunity Research Articles

Phase locked-loop with decaying DC transient removal for three-phase grids

Frequency and phase of the power grid, which are critical for reliable control and protection of grid-tied devices, are generally detected by the closed-loop phase locked-loop (PLL). In highly inductive high-voltage transmission systems, decaying DC (DDC) components with large amplitude can be easily introduced by load disturbances and/or grid abnormalities, leading to severe performance degradation of the PLL during the transient. Focusing on this issue, in this paper, modifications to the conventional synchronous reference frame (SRF)-PLL have been made to address the short-term disturbances including the DDC component, and the system operation is divided into the normal state and the DDC-transient state. The SRF-PLL is only adopted for the normal state where the DDC component is negligible. In the presence of a significant DDC component, as well as disturbances including negative-/zero-sequence components and harmonics, the weak effectiveness of the conventional SRF-PLL is proved, and an efficient DDC component extraction method, with a detection time of 0.5 grid cycle, is introduced for the three-phase system. The real-time amplitude and phase of the positive-sequence component can be efficiently extracted via the proposed scheme, by exploiting the transient signal properties in the dq-frame and assuming a constant grid frequency during the short transient. Finally, a proper design of switching logic has been proposed to allow for the fast and precise transition between the normal and the DDC-transient state, thereby ensuring high steady-state accuracy as well as short-term DDC transient immunity. Hardware-in-the-loop based experiments have been used to verify the effectiveness of the proposed PLL technique.

A MHz-Pulse-Transformer Isolated Gate Driver With Signal-Power Integrated Transmission for Medium-Voltage SiC MOSFETs

The conventional isolated gate driver (GD) solution for the medium-voltage (MV) SiC <small>mosfet</small> separates the signal and power transmissions and requires a bulky GD power supply (GDPS). This article presents a signal-power integrated GD for MV SiC <small>mosfet</small>s with a compact footprint. The proposed GD transmits both the pulsewidth modulation (PWM) signal and GD power by 20-MHz modulated class-E resonant flyback converters, where the transmitted GD power can maintain constant within the full PWM duty-cycle range (i.e., 0&#x0025;&#x2013;100&#x0025;). In addition, the PWM signal transmission of the proposed GD achieves a low total propagation delay time &lt; 75 ns by utilizing the fast transient of 20-MHz RFCs and the edge-based envelope detector. A printed-circuit-board-based coreless transformer is integrated into the proposed GD to achieve an insulation voltage higher than 10 kV_RMS and a low coupling capacitance of 5.85 pF. The common-mode transient immunity of proposed GD is higher than 100 V&#x002F;ns, which is beneficial to drive MV SiC <small>mosfet</small>s with high <i>dv&#x002F;dt</i>. The proposed GD does not require additional GDPSs nor fiber-optics, which achieves a smaller size compared to conventional isolated GDs and is promising to be integrated into SiC <small>mosfet</small> module packages. Experimental results on 3.3 kV and 10 kV SiC <small>mosfet</small>s are provided to validate the effectiveness of the proposed GD.

A naturally DNase-free CRISPR-Cas12c enzyme silences gene expression

Used widely for genome editing, CRISPR-Cas enzymes provide RNA-guided immunity to microbes by targeting foreign nucleic acids for cleavage. We show here that the native activity of CRISPR-Cas12c protects bacteria from phage infection by binding to DNA targets without cleaving them, revealing that antiviral interference can be accomplished without chemical attack on the invader or general metabolic disruption in the host. Biochemical experiments demonstrate that Cas12c is a site-specific ribonuclease capable of generating mature CRISPR RNAs (crRNAs) from precursor transcripts. Furthermore, we find that crRNA maturation is essential for Cas12c-mediated DNA targeting. These crRNAs direct double-stranded DNA binding by Cas12c using a mechanism that precludes DNA cutting. Nevertheless, Cas12c represses transcription and can defend bacteria against lytic bacteriophage infection when targeting an essential phage gene. Together, these results show that Cas12c employs targeted DNA binding to provide antiviral immunity in bacteria, providing a native DNase-free pathway for transient antiviral immunity.

Immune responses of patients without cancer recurrence after a cancer vaccine over a long term.

The present study aimed to clarify the humoral and cellular immune responses of patients with cancer who experienced no recurrence over a long term after receiving a cancer vaccine. The immune kinetics were investigated in response to a personalized peptide vaccination (PPV) among 44 Japanese patients without an active tumor at entry to the vaccination: Lung adenocarcinoma (n=11); colon (n=18); and breast cancer (n=15) (9, 10, 12, 8 and 5 patients with stage I, II, III and IV recurrences, respectively). The patients' immunoglobulin G (IgG) and cytotoxic T lymphocyte (CTL) activities were measured using a multiplexed Luminex assay and an interferon-γ release assay, respectively. There were no severe adverse events related to the PPV other than a grade III injection site reaction. A potent boost in IgG or CTL at the end of the 1st vaccination cycle was observed in 77% of the patients (n=84). The IgG levels were sustained throughout the follow-up period, whereas the CTL levels declined and were transient. A total of 37 of the 44 patients (84%) had no recurrence, with a median follow-up of 67.6 months (interquartile range, 45.6-82.8 months). Overall, the PPV induced long-term humoral immunity with transient cellular immunity in the majority of patients with cancer without an active tumor at their entry to the PPV.

Scrub typhus weakens humoral immune responses through suppression of germinal center and B cell activation

Abstract Scrub typhus is a poorly studied, but life-threatening, disease due to uncontrolled growth of Orientia tsutsugamushi bacteria within endothelial cells and phagocytes, in addition to dysregulated Th1 immune responses and inflammation. Cellular and humoral immunity in infected patients and experimental animals are short-lived, and wane within 1–2 years; however, the underlying mechanism of this transient immunity is unclear. No reports have examined splenic germinal center (GC) or B cell activation during this infection. The study objective is to fill this knowledge gap by using endothelium-targeted C57BL/6 mouse models that mimic pathological features of human scrub typhus. Through NanoString, qRT-PCR, and flow cytometry, we found significant repression of key markers crucial for B cell development (CCR7, BAFFR, PAX5) and GC formation (SLAMF1, ICOS-L, CXCR5, BCL-6) in both mild and severe disease outcomes. The widespread impairments in B and T follicular helper (Tfh) cell activation correlated with excessive Th1 cell activation during disease progression. Immunofluorescence staining (B220, CD3, GL7) revealed evidence of GC formation with sublethal infection, but the near absence of organized GCs at late stages of lethal infection, which was consistent with results from our splenic multi-color flow cytometry and serum antigen-specific ELISA assays for IgG isotypes. Ongoing RNA-seq studies for splenic B cells isolated from sub-lethally or lethally infected mice will provide in-depth, B cell-specific insight during infection. In conclusion, this is the first study to show profound alterations in B cell activation and GC formation in murine models, which helps understand “poor” humoral immunity seen with human scrub typhus. Supported by grants from NIH (R01 EY028773 to JS, R01 AI132674 to LS, R21 AI156536 to LS)

A Murine Model of Waning Scrub Typhus Cross-Protection between Heterologous Strains of Orientia tsutsugamushi.

Orientia tsutsugamushi, the etiologic agent of the life-threatening febrile disease scrub typhus, is an obligately intracellular small coccobacillary bacterium belonging to the family Rickettsiaceae and is transmitted by the parasitic larval stage of trombiculid mites. Progress towards a vaccine for protection against scrub typhus has been impeded by characteristics of the pathogen and the infection. There are numerous strains of O. tsutsugamushi in the Asia-Pacific region with geographical overlap. In human cases immunity has been described as poor against heterologous strains of the pathogen, as well as short-lived against the homologous strain, with a mean antibody reversion rate of less than one year. Animal models of cross-protection as well as of deterioration of this cross-protection are needed to enhance understanding of transient immunity to scrub typhus. To build upon current understanding of this ineffective protection we sought to utilize our recently developed models, sublethal intradermal infection followed by challenge via ordinarily lethal hematogenous dissemination. Mice that were initially infected sublethally with O. tsutsugamushi Gilliam strain and were challenged with an ordinarily lethal dose of heterologous Karp strain were protected from death by a robust immune response at one month after the primary infection as evidenced by an abundance of mononuclear cellular infiltrates in target organs such as lung, liver, and kidney; maintenance of body weight; and low bacterial loads in the organs. Waning protection from lethal Karp strain challenge indicated by weight loss mirroring that observed in naïve mice was observed as early as 9 months after primary Gilliam strain infection, and higher bacterial loads, severe disease, and eventual death in some mice was observed after challenge with Karp strain at 14 months post-initial heterologous infection.

Incidence and Durability of SARS-CoV-2 Antibodies in Patients with Cancer and Health Care Workers following the First Wave of the Pandemic.

Background Patients with cancer and health care workers (HCW) are at higher risk for SARS-CoV-2 infection. There are limited data regarding the rate of symptomatic versus asymptomatic infection and subsequent seropositivity in both populations. Methods We performed a prospective study of patients and HCW across two institutions during the first wave of the pandemic to analyze the prevalence of SARS-CoV-2 antibodies, the extent of associated symptoms, and durability of serologic response. Results In 1,953 persons (733 patients and 1,220 HCW), overall seropositivity rates for 3.1% patients (95% CI 2.0–4.7) and 3.7% HCW (95% CI 2.7–4.9, p=0.520), were similar. Each institutions' seropositivity rates were numerically higher in HCW than patients. Non-Hispanic Whites and Asians had lower antibody rates (2.8%, 95% CI 2.0–3.8 and 3.3%, 95% CI 1.2–7.0) compared to Hispanics (6.9%, 95% CI 3.4–12.4) and non-Hispanic Blacks (5.9%, 95% CI 3.3–9.7), p < 0.001. Among persons with a positive SARS-CoV-2 antibody, 87% of patients and 56% of HCW did not recall having had a fever. Among HCW, administrative and technical personnel were most likely to be seropositive. The rate of persistent seropositivity at 3 months was similar between patients and HCW and was not influenced by the reporting of fever, cancer type, or therapy. Conclusion These data suggest that patients are not at higher risk for febrile SARS-CoV-2 infections or more transient immunity than HCWs. Furthermore, racial differences and lack of association with the extent of HCW contact with COVID-19 patients suggest that community rather than hospital virus exposure was a source of many infections.

A 650 kV/μs Common-Mode Resilient CMOS Galvanically Isolated Communication System

This work presents a galvanically isolated chip-to-chip communication system that utilizes laterally coupled resonators in combination with a new differential full-wave receiver architecture. Lateral resonant coupling increases the isolation capability and significantly minimizes the intra-chip coupling capacitance of galvanic isolators beyond the limits of vertical coupling in standard CMOS. The presented system marries the merits of a laterally resonant coupled channel with a source-gate coupled low-power, low-latency RF detector architecture that enables high common-mode and differential noise immunity. A center-tapped transformer is used as the interface between the proposed fully differential receiver and the communication channel to further enhance the common-mode transient immunity (CMTI). The proposed system is integrated in a 0.25 μm CMOS process with four metal layers and does not alter the native process or necessitate additional fabrication steps. The design does not require exotic packaging and achieves state-of-art CMTI of 650 kV/μs at 5 kVpk isolation, sub-20ns propagation delay, and maintains a small form-factor of 0.95 mm². The GI system exhibits robust performance to fabrication variations, with less than ±0.3% and ±8% sensitivity to process variation and post-assembly chip distance offset, respectively.

Package-Scale Galvanic Isolators Based on Radio Frequency Coupling: Micro–Antenna Design

This paper presents the design of on-chip micro-antennas for package-scale galvanic isolators based on RF planar coupling. A step-by-step design procedure is proposed, which aims at the maximization of the weak electromagnetic coupling between the RX and TX antennas integrated on side-by-side co-packaged chips to enable both high isolation rating and common-mode transient immunity thanks to the high dielectric strength and low capacitive parasitics of a molding compound-based galvanic barrier, respectively. Micro-antenna design guidelines are drawn, highlighting the main relationship between coil coupling performance and their layout parameters, which are often in contrast with respect to traditional integrated inductor ones.

Immunopathology in Lungs after Intranasal Challenge with Live Virus in EHV-1 Recovered Murine Model of EHV-1 Infection: Lessons Learned From Unexpected Findings

Equine herpes virus (EHV-1) causes wide-spread infection among horses worldwide. Virus causes respiratory disease, abortion, neonatal death, paresis, retinopathy, viramea and becomes latent. Horses show transient immunity after EHV-1 infection, where immune responses have been observed to decline after a few months of infection and recovered horses are prone to EHV-1 reinfection. Due to transient immune responses, effective and lasting vaccination to EHV-1 remains a challenge. In an HSV murine model, mice provides solid protection and recovered mice could not be re-infected. In this study we infected mice with EHV-1 intra nasally and after five months, mice were re-infected with EHV-1 along with the previously placebo control. It was expected that mice that had recovered would show some level of protection, but in fact they showed unexpectedly severe clinical signs and more deaths on reinfection. Reinfected mice showed severe breathing difficulties, abdominal breathing, weight loss and death compared to mice infected for the first time. The answers to the worst clinical signs came from post-mortem and histopathological findings. Lungs of challenged mice showed severe consolidation and profound infiltration of inflammatory cells such that the normal parenchyma and architecture of lungs were completely lost. The results of this study suggest that immunoreactive pathological mechanisms exists and should be considered in designing intranasal vaccine preparation for EHV-1 and possibly for other respiratory infections.

A Small Footprint Digital Isolator Based on CMOS Integrated Hall-Effect Sensor

Digital isolators have been widely used to protect low voltage electronics as well as human safety from high voltage surges. However, conventional isolation links occupy large chip areas. In this article, a novel small-size on- chip digital isolator for medium-bitrate application based on a CMOS integrated Hall-effect sensor is reported. With the proposed approach, the area of the transmitter coil is reduced to lower than 50% of conventional transformers. The architecture reduces the chip area in isolation amplifiers, power control units, DC-DC converters, and clock recovery circuits. It allows the integration of multichannel isolators using two custom integrated circuits with no post-processing. The tested prototype achieves a data transfer rate of 20 Mbps with above 12 kV/ <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{s}$ </tex-math></inline-formula> of common-mode transient immunity (CMTI). It has 900 V of continuous isolation working voltage, 27 ns propagation delay, and consumes 2.3 mA of static current.

No protection seen on challenge with live virus after single intranasal immunization with heat inactivated virus in murine model of EHV-1 infection

Equine herpes virus (EHV-1) causes respiratory disease, abortion, neonatal death, paresis, retinopathy, and latent infection and is wide-spread among equine worldwide. Horses show transient immunity after natural or experimental EHV-1 infection and immune responses to EHV-1 begin to decline after a few months after infection. As a result, recovered horses are prone to subsequent EHV-1 infection. Due to transient immune responses, effective and lasting vaccination remains a challenge. As this virus is widespread among equine, development of effective vaccine is a challenge. We used a murine model to study the efficacy of heat inactivated virus in terms of protection in a challenge study. After 34 days following intranasal inoculation with heat inactivated virus, mice were challenged with live virus along with previously placebo control group. Clinical signs, virus titres, and viraemia were studied in both groups. We noticed that mice on challenge showed more clinical signs at peak of infection but no significant difference in virus titres and infectious centre assay was noted. The results of this study suggest that heat inactivated virus does not provide any protection to challenge dose but in fact these group looked clinically worse. These results are discussed along with the possible mechanism involved in more clinical signs seen on challenge after single dose of intranasal immunization by heat inactivate virus in current communication.

Viremia in Equine Herpes Virus-1 infection and a possible link to Transient Protective Immunity

Equine herpes virus (EHV-1) causes respiratory infections in equine, and results in abortion, paresis, neonatal death, and retinopathy and the virus may become latent following initial infection. Virus entry is via the respiratory route, and the virus replicates in the host in ciliated and non-ciliated epithelial cells of the respiratory tract and in Type 1 and Type 2 pneumocytes in the lung parenchyma. After viral replication in the respiratory system, the virus can become disseminated to other parts of body via viraemic cells. The virus also can cross the placenta which leads to abortion of live or dead fetuses without premonitory signs. Infected horses show transient immunity after natural or experimental infection and immune responses to EHV-1, but the immunoprotective status begins to decline after a few months of active infection. Due to the transient immune response, recovered horses are not immunoprotected and thus are prone to subsequent re-infection. Immunity is not long lived after experimental or natural infection, and as a result the development of an effective vaccine has remained a challenge. In this study viraemic cells were studied in a murine EHV-1 infection model. Mice were infected intranasally and viraemic cells were studied on days three and five which occurs during the peak of the infection. The results of this study may help to identify the nature of viraemic cells and their role in the transient immune response to infection. Buffy coat cells and lungs were removed and stained with a fluorescent antibody test for EHV-1 antigen, and lung specimens were subjected to transmission electron microscopy. Both techniques confirmed the presence of viraemic cells in lung tissues. These viraemic cells were further stained for EHV-1 antigen, and for CD4 or CD8 biomarkers and results are discussed re: pathogenesis of EHV-1 infection, identification of viraemic cells in a murine model and possible link of viraemia to transient immune responses in EHV-1 infection, which demonstrate the validity of this murine model for the investigation of the cytopathologic mechanism and sequelae of EHV manifestation in this model.

Improving the electromagnetic compatibility of electronic products by using response surface methodology and artificial neural network

PurposeThe purpose of this study is to use the Taguchi Method for parametric design in the early stages of product development. electromagnetic compatibility (EMC) issues can be considered in the early stages of product design to reduce counter-measure components, product cost and labor consumption increases due to a number of design changes in the R&D cycle and to accelerate the R&D process.Design/methodology/approachThe three EMC characteristics, including radiated emission, conducted emission and fast transient impulse immunity of power, are considered response values; control factors are determined with respect to the relevant parameters for printed circuit board and mechanical design of the product and peripheral devices used in conjunction with the product are considered as noise factors. The optimal parameter set is determined by using the principal component gray relational analysis in conjunction with both response surface methodology and artificial neural network.FindingsMarket specifications and cost of components are considered to propose an optimal parameter design set with the number of grounded screw holes being 14, the size of the shell heat dissipation holes being 3 mm and the arrangement angle of shell heat dissipation holes being 45 degrees, to dispose of 390 O filters on the noise source.Originality/valueThe optimal parameter set can improve EMC effectively to accommodate the design specifications required by customers and pass test regulations.

Efficacy profile of the CYD-TDV dengue vaccine revealed by Bayesian survival analysis of individual-level phase III data.

Sanofi-Pasteur's CYD-TDV is the only licensed dengue vaccine. Two phase three trials showed higher efficacy in seropositive than seronegative recipients. Hospital follow-up revealed increased hospitalisation in 2-5- year-old vaccinees, where serostatus and age effects were unresolved. We fit a survival model to individual-level data from both trials, including year 1 of hospital follow-up. We determine efficacy by age, serostatus, serotype and severity, and examine efficacy duration and vaccine action mechanism. Our modelling indicates that vaccine-induced immunity is long-lived in seropositive recipients, and therefore that vaccinating seropositives gives higher protection than two natural infections. Long-term increased hospitalisation risk outweighs short-lived immunity in seronegatives. Independently of serostatus, transient immunity increases with age, and is highest against serotype 4. Benefit is higher in seropositives, and risk enhancement is greater in seronegatives, against hospitalised disease than against febrile disease. Our results support vaccinating seropositives only. Rapid diagnostic tests would enable viable 'screen-then-vaccinate' programs. Since CYD-TDV acts as a silent infection, long-term safety of other vaccine candidates must be closely monitored. Bill & Melinda Gates Foundation, National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Royal Society. NCT01373281 and NCT01374516.

Covid-19 Reinfection Dynamics-Is Immunity Short Lasting? Case Series of Healthcare Workers

The rapidly spreading Covid-19 pandemic resulted in more than 4.7 million cases diagnosed and 78,727 deaths on September 14, 2020. SARS-CoV-2 was first expected to induce a monophasic disease with at least transient immunity. Here we report a case series of five cases of RT-PCR proved reinfection of Covid-19 in health care workers. On returning to work they might experience a Covid-19 “recurrence” or “reactivation” with increased severity of symptoms after a median symptom-free interval requiring hospitalization which raises the question is the immunity short-lasting. Further studies are required to fully understand the effect of Covid-19 on the immunity of humans in the community. J Microbiol Infect Dis 2021; 11(2):105-107.

Low-Cost Soft Error Robust Hardened D-Latch for CMOS Technology Circuit

In this paper, a Soft Error Hardened D-latch with improved performance is proposed, also featuring Single Event Upset (SEU) and Single Event Transient (SET) immunity. This novel D-latch can tolerate particles as charge injection in different internal nodes, as well as the input and output nodes. The performance of the new circuit has been assessed through different key parameters, such as power consumption, delay, Power-Delay Product (PDP) at various frequencies, voltage, temperature, and process variations. A set of simulations has been set up to benchmark the new proposed D-latch in comparison to previous D-latches, such as the Static D-latch, TPDICE-based D-latch, LSEH-1 and DICE D-latches. A comparison between these simulations proves that the proposed D-latch not only has a better immunity, but also features lower power consumption, delay, PDP, and area footprint. Moreover, the impact of temperature and process variations, such as aspect ratio (W/L) and threshold voltage transistor variability, on the proposed D-latch with regard to previous D-latches is investigated. Specifically, the delay and PDP of the proposed D-latch improves by 60.3% and 3.67%, respectively, when compared to the reference Static D-latch. Furthermore, the standard deviation of the threshold voltage transistor variability impact on the delay improved by 3.2%, while its impact on the power consumption improves by 9.1%. Finally, it is shown that the standard deviation of the (W/L) transistor variability on the power consumption is improved by 56.2%.

The effect of passive immunization on the acute phase of infection in a murine model of EHV‐1.

Equine herpes virus 1 causes respiratory infection in equine world-wide. Virus replicates in the respiratory tissues in ciliated and non-ciliated epithelial cells lining the nasal turbinate bones, trachea, bronchi, bronchioles, and type I and type II pneumocytes, and becomes viraemic causing myeloencephalopathy (paresis) and retinopathy. The virus later becomes latent. While active the virus crosses the placenta and leads to abortion of dead or dying foetuses and neonatal death. Infected horses show transient immunity after natural or experimental infection and immune responses to EHV-1 begin to decline after a few months of infection. Due to the transient nature of the immune response, horses are prone to subsequent reinfection and as a result development of an effective vaccine continues to be a challenge till to date. In order to discover the role of neutralizing antibodies in the pathogenesis of EHV-1 infection, we studied the role of neutralizing antibodies in a murine model of infection during the acute stage of infection by passively immunizing mice by the subcutaneous route with a pre-immune or hyperimmune polyclonal rabbit neutralizing serum 24 hours before virus infection. Mice were challenged intranasally with live EHV-1 virus and virus replication in the respiratory tissues was studied on day 3 and 5 post infection (p.i., acute stage of infection). The effect of passive immunization was also studied on viraemia by infectious centers assays from buffy coat cells. Slight reduction in virus titres in the respiratory tissues and level of viraemia was noted on day 3 p.i, but this difference was not significant. However significant reduction was seen in virus titres both in respiratory tissues and on the state of viraemia on day 5 in passively immunized animals compared with the controls given pre-immune sera from the same rabbit. The sera of passively transferred mice were also tested for presence of rabbit neutralizing antibodies on day 3 and 5 (days 4 and 6) of antibody transfer, suggesting that for complete protection neutralizing IgA may be required at the mucosal surface to stop or otherwise inhibit the viral attachment and thereby explain the differences in viral titres. These results of antibody transfer at an acute stage of infection will be discussed in this communication.

Time-dependent heterogeneity leads to transient suppression of the COVID-19 epidemic, not herd immunity

Epidemics generally spread through a succession of waves that reflect factors on multiple timescales. On short timescales, superspreading events lead to burstiness and overdispersion, whereas long-term persistent heterogeneity in susceptibility is expected to lead to a reduction in both the infection peak and the herd immunity threshold (HIT). Here, we develop a general approach to encompass both timescales, including time variations in individual social activity, and demonstrate how to incorporate them phenomenologically into a wide class of epidemiological models through reparameterization. We derive a nonlinear dependence of the effective reproduction number [Formula: see text] on the susceptible population fraction S. We show that a state of transient collective immunity (TCI) emerges well below the HIT during early, high-paced stages of the epidemic. However, this is a fragile state that wanes over time due to changing levels of social activity, and so the infection peak is not an indication of long-lasting herd immunity: Subsequent waves may emerge due to behavioral changes in the population, driven by, for example, seasonal factors. Transient and long-term levels of heterogeneity are estimated using empirical data from the COVID-19 epidemic and from real-life face-to-face contact networks. These results suggest that the hardest hit areas, such as New York City, have achieved TCI following the first wave of the epidemic, but likely remain below the long-term HIT. Thus, in contrast to some previous claims, these regions can still experience subsequent waves.

Durability of Immunity to SARS-CoV-2 and Other Respiratory Viruses.

Even in nonpandemic times, respiratory viruses account for a vast global burden of disease. They remain a major cause of illness and death and they pose a perpetual threat of breaking out into epidemics and pandemics. Many of these respiratory viruses infect repeatedly and appear to induce only narrow transient immunity, but the situation varies from one virus to another. In the absence of effective specific treatments, understanding the role of immunity in protection, disease, and resolution is of paramount importance. These problems have been brought into sharp focus by the coronavirus disease 2019 (COVID-19) pandemic. Here, we summarise what is now known about adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and draw comparisons with immunity to other respiratory viruses, focusing on the longevity of protective responses.