COVID-19 and Postinfection Immunity: Limited Evidence, Many Remaining Questions.
About: This article is published in JAMA.The article was published on 2020-06-09 and is currently open access. It has received 209 citations till now.
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TL;DR: It is shown that SARS-CoV-2 elicits robust, broad and highly functional memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.
1,501 citations
Cites background from "COVID-19 and Postinfection Immunity..."
..., 2020), and similarly, there is limited evidence of reinfection in humans with previously documented COVID-19 (Kirkcaldy et al., 2020)....
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TL;DR: The development of a rapid (less than 5 min), low-cost, easy-to-implement, and quantitative paper-based electrochemical sensor chip to enable the digital detection of SARS-CoV-2 genetic material is reported.
Abstract: A large-scale diagnosis of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is essential to downregulate its spread within as well as across communities and mitigate the current out...
327 citations
TL;DR: Insight into coronavirus immunity can be informed by previous studies of immune responses to non-human coronaviruses, to common cold coronavIRuses, and to SARS-CoV and MERS- coV, as well as by knowledge of what constitutes a protective immune response and also features that might be pathogenic.
270 citations
Cites background from "COVID-19 and Postinfection Immunity..."
...To date, while SARS-CoV-2 RNA has been detected after periods of negative testing, there is no available culture-based evidence confirming reinfection (Kirkcaldy et al., 2020)....
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TL;DR: From the largest US serosurvey to date, it is estimated > 2 million adult New York residents were infected through late March, with substantial disparities, although cumulative incidence remained below herd immunity thresholds.
257 citations
Cites background from "COVID-19 and Postinfection Immunity..."
...interpretation for short- and long-term immunity remain uncertain, as with other infections, antibody prevalence serostudies with validated assays can assess population-level cumulative incidence in the recent past [6-11]....
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TL;DR: This study indicates that wearing a face mask can be effectively combined with social distancing to flatten the epidemic curve and presents a rational way to implement as an NPI to combat COVID-19.
Abstract: Efficient strategies to contain the coronavirus disease 2019 (COVID-19) pandemic are peremptory to relieve the negatively impacted public health and global economy, with the full scope yet to unfold. In the absence of highly effective drugs, vaccines, and abundant medical resources, many measures are used to manage the infection rate and avoid exhausting limited hospital resources. Wearing masks is among the non-pharmaceutical intervention (NPI) measures that could be effectively implemented at a minimum cost and without dramatically disrupting social practices. The mask-wearing guidelines vary significantly across countries. Regardless of the debates in the medical community and the global mask production shortage, more countries and regions are moving forward with recommendations or mandates to wear masks in public. Our study combines mathematical modeling and existing scientific evidence to evaluate the potential impact of the utilization of normal medical masks in public to combat the COVID-19 pandemic. We consider three key factors that contribute to the effectiveness of wearing a quality mask in reducing the transmission risk, including the mask aerosol reduction rate, mask population coverage, and mask availability. We first simulate the impact of these three factors on the virus reproduction number and infection attack rate in a general population. Using the intervened viral transmission route by wearing a mask, we further model the impact of mask-wearing on the epidemic curve with increasing mask awareness and availability. Our study indicates that wearing a face mask can be effectively combined with social distancing to flatten the epidemic curve. Wearing a mask presents a rational way to implement as an NPI to combat COVID-19. We recognize our study provides a projection based only on currently available data and estimates potential probabilities. As such, our model warrants further validation studies.
218 citations
Cites background from "COVID-19 and Postinfection Immunity..."
...Notably, some evidence suggests that COVID-19 infection may not create longterm immunity in some individuals [20]; however, our model assumes that recovered patients cannot regain the infection for the duration of the model....
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References
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TL;DR: Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.
Abstract: Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6–8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.
5,840 citations
TL;DR: The serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal saliva samples from patients with COVID-19, and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 are ascertained.
Abstract: Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.
2,778 citations
TL;DR: The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients and offer vital clinical information during the course of SARS-CoV-2 infection.
Abstract: BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patients remains largely unknown, and the clinical value of antibody testing has not been fully demonstrated. METHODS: 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (nâ
=â
535) collected during hospitalization were tested for total antibodies (Ab), IgM, and IgG against SARS-CoV-2. The dynamics of antibodies with disease progress were analyzed. RESULTS: Among 173 patients, the seroconversion rates for Ab, IgM, and IgG were 93.1%, 82.7%, and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might be due to the lack of blood samples at the later stage of illness. The median seroconversion times for Ab, IgM, and then IgG were days 11, 12, and 4, respectively. The presence of antibodies wasâ
<40% among patients within 1 week of onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM), and 79.8% (IgG) by day 15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15-39. Combining RNA and antibody detection significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (Pâ
<â
.001), even in the early phase of 1 week from onset (Pâ
=â
.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (Pâ
=â
.006). CONCLUSIONS: Antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.
2,223 citations
TL;DR: Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection and some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.
Abstract: Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China. Objective To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management. Design, Setting, and Participants Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020. Exposures Confirmed SARS-CoV-2 infection. Main Outcomes and Measures Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir. Results Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results. Conclusions and Relevance Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.
1,738 citations
TL;DR: It is found that 15 (21.4%) patients experienced a “turn positive” of nucleic acid detection by RT‐PCR test for SARS‐CoV‐2 after two consecutive negative results, which may be related to the false negative of RT‐ PCR test and prolongeducleic acid conversion.
Abstract: A novel coronavirus (COVID‐19) pandemic cause by Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) threatens the world. We read with interest the recent report by Li et al. that included 610 patients with Coronavirus Disease 2019 (COVID‐19). They reported a high false‐negative rate of real‐time reverse transcription polymerase chain reaction (RT‐PCR) results for SARS‐CoV‐2 detection. In addition, recent report regarding SARS‐CoV‐2 “turn positive” in recovered cases with COVID‐19 were published. Here, we studied the characteristics of nucleic acid conversion for SARS‐CoV‐2 from 70 COVID‐19 patients. We found that 15 (21.4%) patients experienced a “turn positive” of nucleic acid detection by RT‐PCR test for SARS‐CoV‐2 after two consecutive negative results, which may be related to the false negative of RT‐PCR test and prolonged nucleic acid conversionThis article is protected by copyright. All rights reserved.
458 citations