Results from a systematic programme of evaluating COVID-19 reinfection cases in the early phase of the pandemic, Singapore.

OBJECTIVES: The objectives of this study were to describe the coronavirus disease caused by SARS-CoV-2 (COVID-19) reinfection evaluation algorithm used in the early phase of the pandemic in Singapore and analyze the clinical and laboratory characteristics of the cases evaluated. METHODS: We performed a retrospective case-control analysis including all COVID-19 cases evaluated for possible reinfection under the local COVID-19 reinfection evaluation programme between 1 June 2020-30 June 2021. Whole genome sequencing (WGS) was used as confirmatory testing. We compared all reinfection ("RI") cases against those who were evaluated but eventually assessed not to be reinfection ("non-RI"). RESULTS: There were 74 possible reinfection cases evaluated through the programme, of which 32 were subsequently classified as RI. There was strong statistical evidence that RI cases had a longer interval between 1st and 2nd episode (mean 297 days; 95%-confidence interval (CI) 267-327) compared to non-RI cases (mean 186 days; 95%-CI 144-228). The cycle threshold (Ct) value of initial polymerase chain rection (PCR) at 2nd episode was also found to be significantly lower in RI cases (mean 23; 95%-CI 20-26) compared to non-RI cases (mean 34; 95%-CI 32-36). There was no significant difference in the proportion of individuals who had fever, acute respiratory symptoms or asymptomatic in both groups. Delta and beta variants were most commonly identified from WGS and provide indication of re-infection as these were not 'wild-type' and were not circulating during the time period of the index infection. CONCLUSIONS: Using a combination of serologic, microbiologic and genomic criteria to evaluate possible reinfection cases is useful and can provide a framework for evaluation that may be modified for future similar situations.

Retrospective review of re-positive qPCR tests for SARS-CoV: do they indicate presence of reinfection?

OBJECTIVE: In 2019, the Coronavirus Disease 2019 (COVID-19) pandemic broke out, caused by the coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Reinfections can be observed with various respiratory viruses, including human coronaviruses. Moreover, they may result from weak or waning initial immune response, reinfection with another genotype/subtype, or the rapid antigenic changes in the virus. The aim of this study was to investigate the likelihood of reinfection in COVID-19 patients that had a positive qPCR test result at least 60 days after a negative test result in patients that were confirmed with COVID-19 on qPCR. MATERIALS AND METHODS: The quantitative polymerase chain reaction (qPCR) results of a total of 105,000 samples that had been obtained between April 1, 2020, and February 1, 2021, in two separate authorized laboratories were retrospectively analyzed. 22 samples from 11 patients included in the study, qPCR tests were repeated for each sample using the Rotorgene Q PCR system with Diagnovital SARS-CoV-2 (RTA Labs, Turkey) Real-Time PCR kits. Positive samples were screened for B.1.1.7 and E484K mutations using the qPCR method on the Rotorgene Q PCR system with Bio-Speedy SARS-CoV-2 Variant Plus kits (Bioeksen Technology, Turkey). RESULTS: The 105,000 individuals comprised 55,614 men and 49,386 women. In the qPCR test, 14,511 (13.82%) individuals were found to be positive for SARS-CoV-2. Of these, 11 (0.076%) patients were included in the study based on the inclusion criteria. Accordingly, the risk of reinfection was calculated as 0.076% (95% confidence interval [CI]: 0.056%-0.096%) and the incidence was 1.04 per 10,000 population (95% CI: 0.62-1.38 per 10,000). No patient was admitted to the intensive care unit or died during both episodes. Moreover, no B.1.1.7 or E484K mutation was detected in any patient. CONCLUSIONS: The high frequency of COVID-19 infection poses serious risks for the development of new variants and the currently used vaccines are likely to lose their efficacy against new variants. To reduce these risks and to be successful in the fight against the pandemic, we suggest compliance with personal protective measures as well as rapid and widespread application of vaccination not only in developed countries but also in the whole world and the modification of currently used vaccines in such a way to fight against newly emerged variants.

Avidity of IgG to SARS-CoV-2 RBD as a Prognostic Factor for the Severity of COVID-19 Reinfection.

The avidity index (AI) of IgG to the RBD of SARS-CoV-2 was determined for 71 patients with a mild (outpatient) course of COVID-19, including 39 primarily and 36 secondarily reinfected, and 92 patients with a severe (hospital) course of COVID-19, including 82 primarily and 10 secondarily infected. The AI was shown to correlate with the severity of repeated disease. In the group of outpatients with a mild course, the reinfected patients had significantly higher median AIs than those with primary infections (82.3% vs. 37.1%, p < 0.0001). At the same time, in patients with a severe course of COVID-19, reinfected patients still had low-avidity antibodies (median AI of 28.4% vs. 25% in the primarily infected, difference not significant, p > 0.05). This suggests that the presence of low-avidity IgG to RBD during reinfection is a negative prognostic factor, in which a patient's risk of developing COVID-19 in a severe form is significantly increased. Thus, patients with IgG of low avidity (AI ≤ 40%) had an 89 ± 20.5% chance of a severe course of recurrent COVID-19, whereas the detection of high-avidity antibodies (AI ≥ 50%) gave a probability of 94 ± 7.9% for a mild course of recurrent disease (p < 0.05).

COVID-19 reinfections among naturally infected and vaccinated individuals.

The protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to the current vaccination or natural infection is a global concern. We aimed to investigate the rate of SARS-CoV-2 infection and its clinical features among infection-naïve, infected, vaccinated, and post-infection-vaccinated individuals. A cohort was designed among icddr,b staff registered for COVID-19 testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). Reinfection cases were confirmed by whole-genome sequencing. From 19 March 2020 to 31 March 2021, 1644 (mean age, 38.4 years and 57% male) participants were enrolled; where 1080 (65.7%) were tested negative and added to the negative cohort. The positive cohort included 750 positive patients (564 from baseline and 186 from negative cohort follow-up), of whom 27.6% were hospitalized and 2.5% died. Among hospitalized patients, 45.9% had severe to critical disease and 42.5% required oxygen support. Hypertension and diabetes mellitus were found significantly higher among the hospitalised patients compared to out-patients; risk ratio 1.3 and 1.6 respectively. The risk of infection among positive cohort was 80.2% lower than negative cohort (95% CI 72.6-85.7%; p < 0.001). Genome sequences showed that genetically distinct SARS-CoV-2 strains were responsible for reinfections. Naturally infected populations were less likely to be reinfected by SARS-CoV-2 than the infection-naïve and vaccinated individuals. Although, reinfected individuals did not suffer severe disease, a remarkable proportion of naturally infected or vaccinated individuals were (re)-infected by the emerging variants.

COVID-19 reinfection after pregnancy.

BACKGROUND: There have been reports of COVID-19 reinfections, but the immunological characterization of these cases is partial. We report a case of reinfection with SARS-CoV-2, where the first infection occurred in the course of late pregnancy. CASE PRESENTATION: On May 27, 2020, a 37-year-old woman gave birth at full term, 3 hours after full dilatation. She developed fever (38.3°C) after delivery. Mild biological anomalies compatible with COVID-19 were observed: lymphopenia, thrombocytopenia, elevated D-Dimers, CRP, and LDH. At 6-month follow-up, she reported having contracted COVID-19 with high fever, rhinorrhea, hand frostbites, cough, headache, dysgeusia and anosmia. CONCLUSIONS: We report a case of COVID-19 reinfection with a first mild infection during late pregnancy and a more aggressive second infection 5 months later.

Occupational risk of SARS-CoV-2 infection and reinfection during the second pandemic surge: a cohort study.

OBJECTIVES: This cohort study including essential workers, assessed the risk and incidence of SARS-CoV-2 infection during the second surge of COVID-19 according to baseline serostatus and occupational sector. METHODS: Essential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralised registry compiling SARS-CoV-2 infections. Primary outcome was the incidence of virologically confirmed infections from serological assessment (between May and September 2020) to 25 January 2021, according to baseline antibody status and stratified by three predefined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others). RESULTS: 10 457 essential workers were included (occupations requiring sustained physical proximity accounted for 3057 individuals, those involving regular brief contact, 3645 and 3755 workers were classified under 'Other essential occupations'). After a follow-up period of over 27 weeks, 5 (0.6%) seropositive and 830 (8.5%) seronegative individuals had a positive SARS-CoV-2 test, with an incidence rate of 0.2 (95% CI 0.1 to 0.6) and 3.2 (95% CI 2.9 to 3.4) cases per person-week, respectively. Incidences were similar across occupational groups. Seropositive essential workers had a 93% reduction in the hazard (HR of 0.07, 95% CI 0.03 to 0.17) of having a positive test during the follow-up with no significant between-occupational group difference. CONCLUSIONS: A 10-fold reduction in the hazard of being virologically tested positive was observed among anti-SARS-CoV-2 seropositive essential workers regardless of their sector of occupation, confirming the seroprotective effect of a previous SARS-CoV2 exposure at least 6 months after infection.

A case with SARS-CoV-2 reinfection from India.

A healthcare worker presented with fever, cough, headache and tested positive by SARS-CoV-2 real time reverse transcriptase polymerase chain reaction (qRT-PCR). He got admitted to hospital and recovered after 14 days. After 2 months, as a screening protocol considering the high risk setup he got tested and again found to be positive for SARS-CoV-2 by qRT-PCR. Our patient had detectable levels of Anti-SARS-CoV-2 IgG antibodies during the reinfection but found negative for Neutralizing antibodies (NAb). Our findings suggest that the person after the initial infection might not develop the desired protective immunity to prevent the reinfection as demonstrated by absence of NAb.

Recurrence of COVID-19 in a Patient With NMO Spectrum Disorder While Treating With Rituximab: A Case Report and Review of the Literature.

INTRODUCTION: In the context of coronavirus disease 2019 (COVID-19) pandemic, patients with neuromyelitis optica spectrum disorder (NMOSD) are vulnerable to develop COVID-19 due to the immunosuppressive therapy. The objective of this study is to describe a known case of NMOSD on rituximab who experienced 2 episodes of COVID-19. CASE REPORT: A 25-year-old woman, a known case of NMOSD on rituximab was diagnosed with asymptomatic COVID-19. Eight months later, following her last infusion of rituximab, she developed moderate COVID-19. After a partial recovery, she exhibited exacerbation of respiratory symptoms leading to readmission and invasive oxygenation. She was eventually discharged home after 31 days. Her monthly neurological evaluation did not reveal evidence of disease activity. She later received intravenous immunoglobulin and the decision was made to start rituximab again. CONCLUSIONS: Our case raises the possibility of persistent virus shedding and reactivation of severe acute respiratory syndrome coronavirus-2 in a patient with NMOSD and rituximab therapy. We aimed to emphasize a precise consideration of management of patients with NMOSD during the COVID-19 pandemic.

Persistence of symptoms after improvement of acute COVID19 infection, a longitudinal study.

With the number of coronavirus disease 2019 (COVID-19) infected patients increasing all over the world, a large number of survivors have reported changes in their quality of life or experienced re-infection. So, we aimed to detect the percentage, type, and risk factors of persistent symptoms after improvement from acute COVID-19 infection and to detect the percentage of COVID-19 re-infection and degree of severity of the second infection. One hundred seventy-two (59 male, 113 female) patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were followed up via mobile phone every 2 months for 8 to 10 months. After recovery, 105 patients (61%) (30 male, 75 female) reported one or more COVID-19 persistent symptoms. Fatigue, dyspnea, and depression were the most common persistent symptoms representing 37.3%, 22%, 22%, respectively. We found that age was independently related to the persistence of symptoms. During the follow-up, six females (3.5%) had laboratory-confirmed COVID-19 re-infection. Their mean age was 35.7 ± 11 years. The mean interval from the complete recovery of the first infection to the onset of the second one was 53 ± 22.2 days and ranged from 30 to 90 days. The second infection was milder in severity than the first infection in 83.33% of cases. There was a high percentage of patients who complained of persistent symptoms after recovery from COVID-19. Fatigue and headache were the most common persistent symptoms. Age was considered a risk factor for persistent symptoms. Re-infection with SARS-CoV-2 can occur after recovery.

Rate and severity of suspected SARS-Cov-2 reinfection in a cohort of PCR-positive COVID-19 patients.

OBJECTIVES: To estimate the burden and severity of suspected reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A retrospective cohort of members of Kaiser Permanente Southern California with PCR-positive SARS-CoV-2 infection between 1st March 2020 and 31st October 2020 was followed through electronic health records for subsequent positive SARS-CoV-2 tests (suspected reinfection) ≥90 days after initial infection, through 31st January 2021. Incidence of suspected reinfection was estimated using the Kaplan-Meier method. Cox proportional hazards models estimated the association of suspected reinfection with demographic and clinical characteristics, hospitalization, and date of initial infection. RESULTS: The cohort of 75 149 was predominantly Hispanic (49 648/75 149, 66.1%) and included slightly more females than males (39 736, 52.9%), with few immunocompromised patients (953, 1.3%); 315 suspected reinfections were identified, with a cumulative incidence at 270 days of 0.8% (95% confidence interval (CI) 0.7-1.0%). Hospitalization was more common at suspected reinfection (36/315, 11.4%) than initial infection (4094/75 149, 5.4%). Suspected reinfection rates were higher in females (1.0%, CI 0.8-1.2% versus 0.7%, CI 0.5-0.9%, p 0.002) and immunocompromised patients (2.1%, CI 1.0-4.2% versus 0.8%, CI 0.7-1.0%, p 0.004), and lower in children than adults (0.2%, CI 0.1-0.4% versus 0.9%, CI 0.7-1.0%, p 0.023). Patients hospitalized at initial infection were more likely to have suspected reinfection (1.2%, CI 0.6-1.7% versus 0.8%, CI 0.7-1.0%, p 0.030), as were those with initial infections later in 2020 (150-day incidence 0.4%, CI 0.2-0.5% September-October versus 0.2%, CI 0.1-0.3% March-May and 0.3%, CI 0.2-0.3% June-August, p 0.008). In an adjusted Cox proportional hazards model, being female (hazard ratio (HR) 1.44, CI 1.14-1.81), adult (age 18-39, HR 2.71, CI 1.38-5.31, age 40-59 HR 2.22, CI 1.12-4.41, age ≥60 HR 2.52, CI 1.23-5.17 versus <18 years), immunocompromised (HR 2.48, CI 1.31-4.68), hospitalized (HR 1.60, CI 1.07-2.38), and initially infected later in 2020 (HR 2.26, CI 1.38-3.71 September-October versus March-May) were significant independent predictors of suspected reinfection. CONCLUSIONS: Reinfection with SARS-CoV-2 is uncommon, with suspected reinfections more likely in women, adults, immunocompromised subjects, and those previously hospitalized for coronavirus 2019 (COVID-19). This suggests a need for continued precautions and vaccination in patients with COVID-19 to prevent reinfection.

A case of COVID-19 reinfection in the UK.

Protective immunity following COVID-19 infection is not yet fully understood. An understanding of COVID-19 reinfection will be key in guiding government and public health policy decisions in the coming months. This report describes two distinct infective episodes of COVID-19 occurring in the same individual, at the time of writing the first published case in the UK. In April 2020 a 25-year-old UK doctor exhibited classical COVID-19 symptoms, including fevers, headaches, and fatigue. A COVID-19 nucleic acid amplification test (NAAT) at the time returned negative. However, a follow-up antibody test in May 2020 returned positive. In October 2020 the same individual exhibited coryzal symptoms and headaches. He was COVID-19 NAAT tested and found to be positive. There was exposure to high viral load prior to reinfection. Overall the second infection was symptomatically milder, with a faster recovery. This evidence for reinfection poses challenges for public health and vaccination efforts to protect against the COVID-19 pandemic.

Proper Assignation of Reactivation in a COVID-19 Recurrence Initially Interpreted as a Reinfection.

A 77-year-old man (case R) with previous diagnosis of a mild COVID-19 episode was hospitalized 35 days later. On day 23 postadmission, he developed a second COVID-19 episode, now severe, and finally died. Initially, case R's COVID-19 recurrence was interpreted as a reinfection due to the exposure to a SARS-CoV-2 RT-PCR-positive roommate. However, whole-genome sequencing indicated that case R's recurrence corresponded to a reactivation of the strain involved in his first episode. Case R's reactivation had major consequences, leading to a more severe episode, and causing subsequent transmission to another 2 hospitalized patients, 1 of them with fatal outcome.