Endemic Human Coronaviruses Research Articles

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-Reactive IgG and Unequal Strain-Specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

With the advance of SARS-CoV-2 vaccines, the outlook for overcoming the global COVID-19 pandemic has improved. However, understanding of immunity and protection offered by the SARS-CoV-2 vaccines against circulating variants of concern (VOC) is rapidly evolving. We investigated the mRNA vaccine-induced antibody responses against the referent WIV04 (Wuhan) strain, circulating variants, and human endemic coronaviruses in 168 naïve and previously infected people at three-time points. Samples were collected prior to vaccination, after the first and after the second doses of one of the two available mRNA-based vaccines. After full vaccination, both naïve and previously infected participants developed comparable robust SARS-CoV-2 specific spike IgG levels, modest IgM and IgA binding antibodies, and varying degrees of HCoV cross-reactive antibodies. However, the strength and frequency of neutralizing antibodies produced in naïve people were significantly lower than in the previously infected group. We also found that 1/3rd of previously infected people had undetectable neutralizing antibodies after the first vaccine dose; 40% of this group developed neutralizing antibodies after the second dose. In all subjects neutralizing antibodies produced against the B.1.351 and P.1 variants were weaker than those produced against the reference and B.1.1.7 strains. Our findings provide support for future booster vaccinations modified to be active against the circulating variants.Funding Information: This study was supported by grants from the National Cancer Institute (U54CA260543 to A.M.de, R.S.B, and L.P.) and National Institutes of Health, Allergy and Infectious Diseases (U01AI151788 to A.M.de and L.P).Competing Interest: None to declare. Ethics Approval Statement: The study was approved by the George Washington University IRB#: NCR202406. All ED HCP personnel who chose to participate in this study provided written informed consent.

HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients.

The inability of patients with CVID to mount specific antibody responses to pathogens has raised concerns on the risk and severity of SARS-CoV-2 infection, but there might be a role for protective T cells in these patients. SARS-CoV-2 reactive T cells have been reported for SARS-CoV-2 unexposed healthy individuals. Until now, there is no data on T cell immunity to SARS-CoV-2 infection in CVID. This study aimed to evaluate reactive T cells to human endemic corona viruses (HCoV) and to study pre-existing SARS-CoV-2 reactive T cells in unexposed CVID patients. We evaluated SARS-CoV-2- and HCoV-229E and –OC43 reactive T cells in response to seven peptide pools, including spike and nucleocapsid (NCAP) proteins, in 11 unexposed CVID, 12 unexposed and 11 post COVID-19 healthy controls (HC). We further characterized reactive T cells by IFNγ, TNFα and IL-2 profiles. SARS-CoV-2 spike-reactive CD4+ T cells were detected in 7 of 11 unexposed CVID patients, albeit with fewer multifunctional (IFNγ/TNFα/IL-2) cells than unexposed HC. CVID patients had no SARS-CoV-2 NCAP reactive CD4+ T cells and less reactive CD8+ cells compared to unexposed HC. We observed a correlation between T cell reactivity against spike of SARS-CoV-2 and HCoVs in unexposed, but not post COVID-19 HC, suggesting cross-reactivity. T cell responses in post COVID-19 HC could be distinguished from unexposed HC by higher frequencies of triple-positive NCAP reactive CD4+ T cells. Taken together, SARS-CoV-2 reactive T cells are detectable in unexposed CVID patients albeit with lower recognition frequencies and polyfunctional potential. Frequencies of triple-functional reactive CD4+ cells might provide a marker to distinguish HCoV cross-reactive from SARS-CoV-2 specific T cell responses. Our data provides evidence, that anti-viral T cell immunity is not relevantly impaired in most CVID patients.

SARS-CoV-2 Re-infections: Lessons from Other Coronaviruses

Animal and human endemic coronaviruses have been known for decades, as has their capacity to re-infect. In the COVID-19 pandemic, it is key to reveal the factors that influence reinfection susceptibility. In this commentary, I provide a view on endemic animal and human coronaviruses and the correlates of protection to reinfection.

Convalescent Memory T Cell Immunity in Individuals with Mild or Asymptomatic SARS-CoV-2 Infection May Result from an Evolutionarily Adapted Immune Response to Coronavirus and the 'Common Cold'.

Recent studies have shown a significant level of T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in convalescent coronavirus disease 2019 (COVID-19) patients and unexposed healthy individuals. Also, SARS-CoV-2-reactive T memory cells occur in unexposed healthy individuals from endemic coronaviruses that cause the ‘common cold.’ The finding of the expression of adaptive SARS-CoV-2-reactive T memory cells in unexposed healthy individuals may be due to multiple cross-reactive viral protein targets following previous exposure to endemic human coronavirus infections. The opinion of the authors is that determination of protein sequence homologies across seemingly disparate viral protein libraries may provide epitope-matching data that link SARS-CoV-2-reactive T memory cell signatures to prior administration of cross-reacting vaccines to common viral pathogens. Exposure to SARS-CoV-2 initiates diverse cellular immune responses, including the associated ‘cytokine storm’. Therefore, it is possible that the intact virus possesses a required degree of conformational matching, or stereoselectivity, to effectively target its receptor on multiple cell types. Therefore, conformational matching may be viewed as an evolving mechanism of viral infection and viral replication by an evolutionary modification of the angiotensin-converting enzyme 2 (ACE2) receptor required for SARS-CoV-2 binding and host cell entry. The authors propose that convalescent memory T cell immunity in individuals with mild or asymptomatic SARS-CoV-2 infection may result from an evolutionarily adapted immune response to coronavirus and the ‘common cold’.

Complicating Infections Associated with Common Endemic Human Respiratory Coronaviruses.

Coronaviruses OC43, 229E, NL63, and HKU1 are endemic human respiratory coronaviruses that typically cause mild to moderate upper respiratory infections, similar to the common cold. They also may cause simple and complicated lower respiratory infections, otitis media, asthma exacerbations, gastroenteritis, and a few systemic complications. These viruses are usually seasonal (with winter dominance) and affect nearly all age groups. The seasonal and annual variation in virus prevalence has implications for understanding the concept of acquired immunity and its persistence or diminution. Coronaviruses generally have outbreak potential in susceptible populations of any age, particularly in patients with comorbidities, who tend to have increased clinical disease. These 4 coronaviruses are often found in the context of what appears to be coinfection with other pathogens, but especially other viruses. If coronaviruses are not specifically tested for, the sole detection of a viral copathogen would suggest the pathogen is the causative agent, when a coronavirus may be culpable, or both. The detection of these viruses in circumstances where respiratory viruses are generally sought in clinical samples is, therefore, justified. These pathogens can be chronically shed from the respiratory tract, which is more likely to occur among immunocompromised and complicated patients. These viruses share the potential for genetic drift. The genome is among the largest of RNA viruses, and the capability of these viruses to further change is likely underestimated. Given the potential disease among humans, it is justified to search for effective antiviral chemotherapy for these viruses and to consider uses in niche situations should effective therapy be defined. Whereas SARS-CoV-2 may follow the epidemiological pattern of SARS-CoV and extinguish slowly over time, there is yet concern that SARS-CoV-2 may establish itself as an endemic human respiratory coronavirus similar to OC43, 2299E, NL63, and HKU1. Until sufficient data are acquired to better understand the potential of SARS-CoV-2, continued work on antiviral therapy and vaccination is imperative.

Applying Immune Instincts and Maternal Intelligence from Comparative Microbiology to COVID-19.

New data specific to COVID-19 are emerging quickly on key issues of immunity and prevention, but past research in coronavirology and for other human pathogens (e.g., Mycoplasma pneumoniae) has been available and of great relevance. Considerable study of endemic human coronaviruses has shown that neutralizing antibody correlates with protection, but effective clinical protection is variable for subsequent virus exposure. Animal coronavirus research has emphasized the importance of local mucosal protection (especially IgA) and systemic responses. Animal model and human post-infection studies for SARS-CoV and MERS-CoV are largely corroborative. Whether for passive therapeutic strategies or vaccination, these findings provide a template for COVID-19. Many approaches to vaccination have emerged, and there may be more than one vaccine that will be applied, but individualized obstacles and concerns for administration, efficacy, and safety are inevitable. Regardless of safeguards or promises that may be understood from laboratory or vertebrate experiments, observations from large-scale human trials will ultimately prove to shape the medical future. Focus on common mucosal immunity can be underrated, and equally or more, focus on lactogenic immunity may be underestimated. In understanding both passive immunity and protection, the body is already primed to educate us with decisions of what constitutes protection and harm. This review provides key insights that drive hypotheses into how the instinct of immunity and the intelligence of the maternal component of the common mucosal immune system has already guided us and may continue to do so effectively into a bright and safe future.

Endemic Non–SARS-CoV-2 Human Coronaviruses in a Community-Based Australian Birth Cohort

The coronavirus (CoV) disease 2019 pandemic has drawn attention to the CoV virus family. However, in community settings, there is limited information on these viruses in healthy children. We explored the epidemiology of the 4 endemic (non-severe acute respiratory syndrome CoV 2) human coronaviruses (HCoVs) by species, including acute illness episodes, risk factors, and health care burden in Australian children in the first 2 years of life. The Observational Research in Childhood Infectious Diseases community-based cohort was a prospective study of acute respiratory illnesses in children from birth until their second birthday. Parents recorded daily symptoms, maintained an illness-burden diary, and collected weekly nasal swabs, which were tested for 17 respiratory viruses, including HCoVs, by real-time polymerase chain reaction assays. Overall, 158 children participating in Observational Research in Childhood Infectious Diseases provided 11 126 weekly swabs, of which 168 were HCoV-positive involving 130 incident episodes. HCoV-NL63 and HCoV-OC43 were most commonly detected, accounting for two-thirds of episodes. Whereas 30 children had different HCoVs detected on different occasions, 7 were reinfected with the same species. HCoV incidence in the first 2 years of life was 0.76 episodes per child-year (95% confidence interval [CI] 0.63 to 0.91), being greatest in the second year (1.06; 95% CI 0.84 to 1.33) and during winter (1.32; 95% CI 1.02 to 1.71). Fifty percent of HCoV episodes were symptomatic, and 24.2% led to health care contact. In children, HCoV infections are common, recurrent, and frequently asymptomatic. In future studies, researchers should determine transmission pathways and immune mechanisms.

Les Coronavirus humains

Four coronaviruses cause frequent and most often mild respiratory infections in humans: HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU 1. In addition to these endemic human coronaviruses, three new coronaviruses of zoonotic origin have emerged in the human population over the past 20 years. SARS-CoV (-1) appeared in 2003, MERS-CoV appeared in 2012, and SARS-CoV-2 appeared in 20l9. These three coronaviruses are the causative agents of a severe respiratory syndrome. The epidemic of the severe acute respiratory syndrome (SARS) due to SARS-CoV-l affected approximately 8,000 individuals and caused approximately 800 deaths but was brought under control within a few months. MERS-CoV has caused more than 2,500 cases since 20l2 with a mortality of around 35 %. SARS-CoV-2 is currently responsible for a major pandemic with significant mortality in the elderly or in patients with underlying diseases.

T-cell responses to MERS coronavirus infection in people with occupational exposure to dromedary camels in Nigeria: an observational cohort study

BackgroundMiddle East respiratory syndrome (MERS) remains of global public health concern. Dromedary camels are the source of zoonotic infection. Over 70% of MERS coronavirus (MERS-CoV)-infected dromedaries are found in Africa but no zoonotic disease has been reported in Africa. We aimed to understand whether individuals with exposure to dromedaries in Africa had been infected by MERS-CoV.MethodsWorkers slaughtering dromedaries in an abattoir in Kano, Nigeria, were compared with abattoir workers without direct dromedary contact, non-abattoir workers from Kano, and controls from Guangzhou, China. Exposure to dromedaries was ascertained using a questionnaire. Serum and peripheral blood mononuclear cells (PBMCs) were tested for MERS-CoV specific neutralising antibody and T-cell responses.FindingsNone of the participants from Nigeria or Guangdong were MERS-CoV seropositive. 18 (30%) of 61 abattoir workers with exposure to dromedaries, but none of 20 abattoir workers without exposure (p=0·0042), ten non-abattoir workers or 24 controls from Guangzhou (p=0·0002) had evidence of MERS-CoV-specific CD4+ or CD8+ T cells in PBMC. T-cell responses to other endemic human coronaviruses (229E, OC43, HKU-1, and NL-63) were observed in all groups with no association with dromedary exposure. Drinking both unpasteurised camel milk and camel urine was significantly and negatively associated with T-cell positivity (odds ratio 0·07, 95% CI 0·01–0·54).InterpretationZoonotic infection of dromedary-exposed individuals is taking place in Nigeria and suggests that the extent of MERS-CoV infections in Africa is underestimated. MERS-CoV could therefore adapt to human transmission in Africa rather than the Arabian Peninsula, where attention is currently focused.FundingThe National Science and Technology Major Project, National Institutes of Health.

Surveillance of endemic human coronaviruses (HCoV-NL63, OC43 and 229E) associated with childhood pneumonia in Kilifi, Kenya.

Introduction: Human coronaviruses (HCoVs) circulate endemically in human populations, often with seasonal variation. We describe the long-term patterns of paediatric disease associated with three of these viruses, HCoV-NL63, OC43 and 229E, in coastal Kenya. Methods: Continuous surveillance of pneumonia admissions was conducted at the Kilifi county hospital (KCH) located in the northern coastal region of Kenya. Children aged <5 years admitted to KCH with clinically defined syndromic severe or very severe pneumonia were recruited. Respiratory samples were taken and tested for 15 virus targets, using real-time polymerase chain reaction. Unadjusted odds ratios were used to estimate the association between demographic and clinical characteristics and HCoV positivity. Results: From 2007 to 2019, we observed 11,445 pneumonia admissions, of which 314 (3.9%) tested positive for at least one of the HCoV types surveyed in the study. There were 129 (41.1%) OC43, 99 (31.5%) 229E, 74 (23.6%) NL63 positive cases and 12 (3.8%) cases of HCoV to HCoV coinfection. Among HCoV positive cases, 47% (n=147) were coinfected with other respiratory virus pathogens. The majority of HCoV cases were among children aged <1 year (66%, n=208), though there was was no change in the proportion infected by age. HCoV-OC43 was predominant of the three HCoV types throughout the surveillance period. Evidence for seasonality was not identified. Conclusions: Overall, 4% of paediatric pneumonia admissions were associated with three endemic HCoVs, with a high proportion of cases co-occurring with another respiratory virus, no clear seasonal pattern, and with the age-distribution of cases following that of pneumonia admissions (i.e. highest in infants). These observations suggest, at most, a small severe disease contribution of endemic HCoVs in this tropical setting and offer insight into their potential future burden and epidemiological characteristics.

A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity

Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.

Surveillance of endemic human coronaviruses (HCoV-NL63, OC43 and 229E) associated with childhood pneumonia in Kilifi, Kenya

Introduction: Human coronaviruses (HCoVs) circulate endemically in human populations, often with seasonal variation. We describe the long-term patterns of paediatric disease associated with three of these viruses, HCoV-NL63, OC43 and 229E, in coastal Kenya. Methods: Continuous surveillance of pneumonia admissions was conducted at the Kilifi county hospital (KCH) located in the northern coastal region of Kenya. Children aged <5 years admitted to KCH with clinically defined syndromic severe or very severe pneumonia were recruited. Respiratory samples were taken and tested for 15 virus targets, using real-time polymerase chain reaction. Unadjusted odds ratios were used to estimate the association between demographic and clinical characteristics and HCoV positivity. Results: From 2007 to 2019, we observed 11,445 pneumonia admissions, of which 314 (3.9%) tested positive for at least one of the HCoV types surveyed in the study. There were 129 (41.1%) OC43, 99 (31.5%) 229E, 74 (23.6%) NL63 positive cases and 12 (3.8%) cases of HCoV to HCoV coinfection. Among HCoV positive cases, 47% (n=147) were coinfected with other respiratory virus pathogens. The majority of HCoV cases were among children aged <1 year (66%, n=208), though there was was no change in the proportion infected by age. HCoV-OC43 was predominant of the three HCoV types throughout the surveillance period. Evidence for seasonality was not identified. Conclusions: Overall, 4% of paediatric pneumonia admissions were associated with three endemic HCoVs, with a high proportion of cases co-occurring with another respiratory virus, no clear seasonal pattern, and with the age-distribution of cases following that of pneumonia admissions (i.e. highest in infants). These observations suggest, at most, a small severe disease contribution of endemic HCoVs in this tropical setting and offer insight into their potential future burden and epidemiological characteristics.

SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved. Here we investigated CD4+ T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors. We detected spike-reactive CD4+ T cells not only in 83% of patients with COVID-19 but also in 35% of healthy donors. Spike-reactive CD4+ T cells in healthy donors were primarily active against C-terminal epitopes in the spike protein, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared with N-terminal epitopes. Spike-protein-reactive T cell lines generated from SARS-CoV-2-naive healthy donors responded similarly to the C-terminal region of the spike proteins of the human endemic coronaviruses 229E and OC43, as well as that of SARS-CoV-2. This results indicate that spike-protein cross-reactive T cells are present, which were probably generated during previous encounters with endemic coronaviruses. The effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined in larger cohorts. However, the presence of spike-protein cross-reactive T cells in a considerable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming trials investigating COVID-19 vaccines.

Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Test

Nucleic acid amplification tests (NAATs) are the primary means of identifying acute infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accurate and fast test results may permit more efficient use of protective and isolation resources and allow rapid therapeutic interventions. We evaluated the analytical and clinical performance characteristics of the Xpert Xpress SARS-CoV-2 (Xpert) test, a rapid, automated molecular test for SARS-CoV-2. Analytical sensitivity and specificity/interference were assessed with infectious SARS-CoV-2; other infectious coronavirus species, including SARS-CoV; and 85 nasopharyngeal swab specimens positive for other respiratory viruses, including endemic human coronaviruses (hCoVs). Clinical performance was assessed using 483 remnant upper- and lower-respiratory-tract specimens previously analyzed by standard-of-care (SOC) NAATs. The limit of detection of the Xpert test was 0.01 PFU/ml. Other hCoVs, including Middle East respiratory syndrome coronavirus, were not detected by the Xpert test. SARS-CoV, a closely related species in the subgenus Sarbecovirus, was detected by a broad-range target (E) but was distinguished from SARS-CoV-2 (SARS-CoV-2-specific N2 target). Compared to SOC NAATs, the positive agreement of the Xpert test was 219/220 (99.5%), and the negative agreement was 250/261 (95.8%). A third tie-breaker NAAT resolved all but three of the discordant results in favor the Xpert test. The Xpert test provided sensitive and accurate detection of SARS-CoV-2 in a variety of upper- and lower-respiratory-tract specimens. The high sensitivity and short time to results of approximately 45 min may impact patient management.

Surveillance of endemic human coronaviruses (HCoV-NL63, OC43 and 229E) associated with pneumonia in Kilifi, Kenya

Introduction: Human coronaviruses (HCoVs) circulate endemically in human populations, often with seasonal variation. We describe the long-term patterns of paediatric disease associated with three of these viruses, HCoV-NL63, OC43 and 229E, in coastal Kenya. Methods: Continuous surveillance of pneumonia admissions was conducted at the Kilifi county hospital (KCH) located in the northern coastal region of Kenya. Children aged <5 years admitted to KCH with clinically defined syndromic severe or very severe pneumonia were recruited. Respiratory samples were taken and tested for 15 virus targets, using real-time polymerase chain reaction. Unadjusted odds ratios were used to estimate the association between demographic and clinical characteristics and HCoV positivity. Results: From 2007 to 2019, we observed 11,445 pneumonia admissions, of which 314 (3.9%) tested positive for at least one of the HCoV types surveyed in the study. There were 129 (41.1%) OC43, 99 (31.5%) 229E, 74 (23.6%) NL63 positive cases and 12 (3.8%) cases of HCoV to HCoV coinfection. Among HCoV positive cases, 47% (n=147) were coinfected with other respiratory virus pathogens. The majority of HCoV cases were among children aged <1 year (66%, n=208), though there was was no change in the proportion infected by age. HCoV-OC43 was predominant of the three HCoV types throughout the surveillance period. Evidence for seasonality was not identified. Conclusions: Overall, 4% of paediatric pneumonia admissions were associated with three endemic HCoVs, with a high proportion of cases co-occurring with another respiratory virus, no clear seasonal pattern, and with the age-distribution of cases following that of pneumonia admissions (i.e. highest in infants). These observations suggest, at most, a small severe disease contribution of endemic HCoVs in this tropical setting and offer insight into their potential future burden and epidemiological characteristics.

COVID-19: Precautionary Guidelines for Ophthalmologists.

Several coronaviruses can infect humans, and the globally endemic human coronaviruses, HCoV-229E (human coronavirus 229E), HCoV-NL63 (human coronavirus NL63), and others, tend to cause mild respiratory diseases. The zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus type1 (SARS-CoV-1) have high fatality rates. In December 2019, the World Health Organization (WHO) was notified by Chinese authorities about an outbreak of pneumonia before the causative organism was identified in January 2020 as a novel coronavirus family. The WHO refers to the virus as coronavirus disease 2019 (COVID-19). Within several weeks, the outbreak has become an emergency, and many countries have since been affected. The method of transmission is not yet fully known but is thought to be mainly respiratory. Healthcare providers, particularly ophthalmologists, are at high risk of a COVID-19 infection through unprotected contact with eye secretions during routine ophthalmic examinations that involve the use of direct ophthalmoscopy and slit-lamp examinations, which are usually performed in a setting that allows for close doctor-patient contact. In light of these, specific measures are needed from an ophthalmic point of view to control the COVID-19 outbreak and to protect health care providers.

Features of enteric disease from human coronaviruses: Implications for COVID-19.

Coronaviruses have long been studied in both human and veterinary fields. Whereas the initial detection of endemic human respiratory coronaviruses was problematic, detection of these and newly discovered human coronaviruses has been greatly facilitated with major advances in the laboratory. Nevertheless, technological factors can affect the accuracy and timeliness of virus detection. Many human coronaviruses can be variably found in stool samples. All human coronaviruses have been variably associated with symptoms of gastroenteritis. Coronaviruses can occasionally be cultured from enteric specimens, but most detection is accomplished with genetic amplification technologies. Excretion of viral RNA in stool can extend for a prolonged period. Culture‐positive stool samples have been found to exceed a fourteen day period after onset of infection for some coronaviruses. Virus can also sometimes be cultured from patients' respiratory samples during the late incubation period. Relatively asymptomatic patients may excrete virus. Both viable and nonviable virus can be found in the immediate environment of the patient, the health care worker, and less often the public. These lessons from the past study of animal and human coronaviruses can be extended to presumptions for severe acute respiratory syndrome coronavirus 2. Already, the early reports from the coronavirus disease‐2019 pandemic are confirming some concerns. These data have the cumulative potential to cause us to rethink some current and common public health and infection control strategies.

COVID-19 in Spain: Transplantation in the midst of the pandemic.

Spain has been one of the most affected countries by the COVID‐19 outbreak. As of April 28, 2020, the number of confirmed cases is 210 773, including 102 548 patients recovered, more than 10 300 admitted to the ICU, and 23 822 deaths, with a global case fatality rate of 11.3%. From the perspective of donation and transplantation, the Spanish system first focused on safety issues, providing recommendations for donor evaluation and testing, and to rule out SARS‐CoV‐2 infection in potential recipients prior to transplantation. Since the country entered into an epidemiological scenario of sustained community transmission and saturation of intensive care, developing donation and transplantation procedures has become highly complex. Since the national state of alarm was declared in Spain on March 13, 2020, the mean number of donors has declined from 7.2 to 1.2 per day, and the mean number of transplants from 16.1 to 2.1 per day. Increased mortality on the waiting list may become a collateral damage of this terrible pandemic.

Back to the basics: Diluted bleach for COVID-19

To the Editor: Since December 2019, COVID-19. a highly pathogenic novel human coronavirus severe acute respiratory syndrome coronavirus (SARS-Cov-2), has emerged from China harboring high human-to-human transmission rates and persistence on inanimate surfaces.1Kampf G. Todt D. Pfaender S. Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.J Hosp Infect. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2121) Google Scholar An analysis of 22 studies revealed that human coronaviruses similar to COVID-19, including SARS coronavirus, Middle East respiratory syndrome (MERS) coronavirus, and endemic human coronaviruses (HCoV), can persist on inanimate surfaces, such as metal, glass, or plastic, for up to 9 days, but are efficiently inactivated by 62% to 71% ethanol, 0.5% hydrogen peroxide, or 0.1% sodium hypochlorite within 1 minute.1Kampf G. Todt D. Pfaender S. Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.J Hosp Infect. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2121) Google Scholar A study by van Doremalen et al2van Doremalen N. Bushmaker T. Morris D.H. et al.Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1.N Engl J Med. 2020; Crossref Scopus (5624) Google Scholar evaluating the stability of COVID-19 and SARS-CoV-1 suggests that COVID-19 may remain viable for hours to days on surfaces made from a variety of materials. To help identify commercial disinfectants against COVID-19, the United States Environmental Protection Agency (EPA) has created a list of adequate products by their EPA registration number.3United States Environmental Protection AgencyPesticide Registration. List N: disinfectants for Use Against SARS-CoV-2.https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2Date: 2020Date accessed: March 20, 2020Google Scholar Unfortunately, with exponentially rising COVID-19 cases in the United States, commercial disinfect supplies are in high demand and will unquestionably be limited in the near future. We will have to get creative with available resources, all the while taking safe precautions to ensure our efforts improve and not worsen the ongoing situation. Various dilutions of sodium hypochlorite, effectively Dakin's solution, have been tried and true in dermatology and wound care for many years. To achieve the formulation noted by Kampf et al,1Kampf G. Todt D. Pfaender S. Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.J Hosp Infect. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2121) Google Scholar ∼0.1% sodium hypochlorite can be made by a roughly 1:50 dilution of household bleach (∼5.25% to 6% sodium hypochlorite) in tap water. Although the Kampf et al analysis is a combination of non–COVID-19 studies, we expect the proposed formulation to similarly also disinfect surfaces of the novel coronavirus. The Centers for Disease Control and Prevention (CDC) also recommends an approximately 1:50 dilution to disinfect COVID-19, explicitly noting 5 tablespoons (one-third cup) bleach per gallon of water or 4 teaspoons bleach per quart of water.4Centers for Disease Control and PreventionClean & Disinfect-Coronavirus Disease 2019: interim Recommendations for U.S. Households with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19).https://www.cdc.gov/coronavirus/2019-ncov/prepare/cleaning-disinfection.htmlDate accessed: March 20, 2020Google Scholar Different dilutions of sodium hypochlorite can vary in their in vivo fibroblast and keratinocyte cytotoxicity; however, dilutions of ∼0.1% sodium hypochlorite are clinically effective with minimal irritation or sensitization.5Ronco C. Mishkin G.J. Disinfection by Sodium Hypochlorite: Dialysis Applications. Karger, Basel, Switzerland2007Google Scholar One should be mindful that corrosive injury on mucous membrane/skin contact is possible with excess volumes or mishandling, so appropriate caution and moderation is necessary.6Slaughter R.J. Watts M. Vale J.A. Grieve J.R. Schep L.J. The clinical toxicology of sodium hypochlorite.Clin Toxicol (Phila). 2019; 57: 303-311Crossref PubMed Scopus (66) Google Scholar This solution should ideally be used within 1 month of preparation and stored in a closed, opaque container at room temperature.7National Research Council (US) and Institute of Medicine (US)Panel on Needle Exchange and Bleach Distribution Programs.in: Normand J. Vlahov D. Moses L.E. Preventing HIV Transmission: The Role of Sterile Needles and Bleach. National Academies Press (US), Washington, DC1995Google Scholar While the exact viral load on inanimate surfaces is unknown during an outbreak, it is critical to disinfect frequently touched surfaces.1Kampf G. Todt D. Pfaender S. Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents.J Hosp Infect. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2121) Google Scholar With rapidly diminishing availability of commercial cleaning supplies, simple diluted bleach, which is readily available, can effectively disinfect our clinics, homes, and environment to prevent sustained transmission from inanimate objects. As with many disinfectants, minimizing long-term skin contact and ensuring good ventilation can minimize clinical toxicity. In Henry Dakin's spirit, we should strive to share with our colleagues the cost-effective, accessible, and relatively safe power of diluted bleach.

Covid-19 Immune Signatures Reveal Stable Antiviral T-Cell Function Despite Declining Humoral Responses

To investigate the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell immunity and its relationship with antibody levels and pre-existing immunity against endemic human coronaviruses (huCoV) during disease and beyond, we analyzed patients with recovered (RC, n=178) and active Coronavirus Disease-2019 (COVID-19; AC, n=10) and healthy donors (HD, n=58). Overall, ACs had highest SARS-CoV-2 antibody levels against nucleocapsid (N) and spike (S) proteins but reduced antiviral T-cell immunity, whereas in RCs, antibody levels partially correlated with SARS-CoV-2-specific T-cell frequencies. Interestingly, humoral responses declined throughout convalescence, whereas T-cell immunity remained stable. RCs exhibited polyfunctional, mainly IFN-γ-secreting CD4 + effector memory T-cell responses. Humoral and cellular response towards huCoV strains in RCs with strong SARS-CoV-2 T-cell immunity implies a protective role of pre-existing immunity against huCoV. This study provides essential evidence-based data about stable protective T-cell immunity during disease and recovery which is essential to guide diagnosis and treatment of COVID-19.