Highly Sensitive and Specific SARS-CoV-2 Serological Assay Using a Magnetic Modulation Biosensing System.

Sensitive serological assays are needed to provide valuable information about acute and past viral infections. For example, detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies could serve as the basis for an "immunity passport" that would enable individuals to travel internationally. Here, utilizing a novel Magnetic Modulation Biosensing (MMB) system and the receptor-binding domain of the SARS-CoV-2 spike protein, we demonstrate a highly sensitive and specific anti-SARS-CoV-2 IgG serological assay. Using anti-SARS-CoV-2 IgG antibodies, RT-qPCR SARS-CoV-2-positive and healthy patients' samples, and vaccinees' samples, we compare the MMB-based SARS-CoV-2 IgG assay's analytical and clinical sensitivities to those of the enzyme-linked immunosorbent assay (ELISA). Compared with ELISA, the MMB-based assay has an ~6-fold lower limit of detection (129 ng/L vs. 817 ng/L), and it detects an increase in the IgG concentration much earlier after vaccination. Using 85 RT-qPCR SARS-CoV-2-positive samples and 79 -negative samples, the MMB-based assay demonstrated similar clinical specificity (98% vs. 99%) and sensitivity (93% vs. 92%) to the ELISA test, but with a much faster turnaround time (45 min vs. 245 min). The high analytical and clinical sensitivity, short turnaround time, and simplicity of the MMB-based assay makes it a preferred method for antibody detection.

The Role of NS1 Protein in the Diagnosis of Flavivirus Infections.

Nonstructural protein 1 (NS1) is a glycoprotein among the flavivirus genus. It is found in both membrane-associated and soluble secreted forms, has an essential role in viral replication, and modulates the host immune response. NS1 is secreted from infected cells within hours after viral infection, and thus immunodetection of NS1 can be used for early serum diagnosis of dengue fever infections instead of real-time (RT)-PCR. This method is fast, simple, and affordable, and its availability could provide an easy point-of-care testing solution for developing countries. Early studies show that detecting NS1 in cerebrospinal fluid (CSF) samples is possible and can improve the surveillance of patients with dengue-associated neurological diseases. NS1 can be detected postmortem in tissue specimens. It can also be identified using noninvasive methods in urine, saliva, and dried blood spots, extending the availability and effective detection period. Recently, an enzyme-linked immunosorbent assay (ELISA) assay for detecting antibodies directed against Zika virus NS1 has been developed and used for diagnosing Zika infection. This NS1-based assay was significantly more specific than envelope protein-based assays, suggesting that similar assays might be more specific for other flaviviruses as well. This review summarizes the knowledge on flaviviruses' NS1's potential role in antigen and antibody diagnosis.

The effect of ivermectin on the viral load and culture viability in early treatment of nonhospitalized patients with mild COVID-19 - a double-blind, randomized placebo-controlled trial.

OBJECTIVES: Ivermectin, an antiparasitic agent, also has antiviral properties. In this study, we aimed to assess whether ivermectin has anti-SARS-CoV-2 activity. METHODS: In this double-blinded trial, we compared patients receiving ivermectin for 3 days versus placebo in nonhospitalized adult patients with COVID-19. A reverse transcriptase-polymerase chain reaction from a nasopharyngeal swab was obtained at recruitment and every 2 days for at least 6 days. The primary endpoint was a reduction of viral load on the sixth day as reflected by cycle threshold level >30 (noninfectious level). The primary outcome was supported by the determination of viral-culture viability. RESULTS: Of 867 patients screened, 89 were ultimately evaluated per-protocol (47 ivermectin and 42 placeboes). On day 6, the odds ratio (OR) was 2.62 (95% confidence interval [CI]: 1.09-6.31) in the ivermectin arm, reaching the endpoint. In a multivariable logistic regression model, the odds of a negative test on day 6 were 2.28 times higher in the ivermectin group but reached significance only on day 8 (OR 3.70; 95% CI: 1.19-11.49, P = 0.02). Culture viability on days 2 to 6 was positive in 13.0% (3/23) of ivermectin samples versus 48.2% (14/29) in the placebo group (P = 0.008). CONCLUSION: There were lower viral loads and less viable cultures in the ivermectin group, which shows its anti-SARS-CoV-2 activity. It could reduce transmission in these patients and encourage further studies with this drug.

Corrigendum to "Does ivermectin have a place in the treatment of mild Covid-19?" [New Microbes New Infect 46 (C) (2022 Mar) 100985].

[This corrects the article DOI: 10.1016/j.nmni.2022.100985.].

Head louse infestations before and during the COVID-19 epidemic in Israel.

Head louse infestations caused by Pediculus humanus capitis (Phthiraptera: Pediculidae) are a public health problem in developing and developed countries worldwide. Head to head contact is by far the most common mode of lice transmission. In March 2020, WHO declared the COVID-19 outbreak as a pandemic. Starting from March 2020, the Israeli government established mandatory isolation for extensive periods including closure of school systems for very long time. The aim of the project was to compare the pediculicide sale numbers before the COVID-19 epidemic with those starting of the epidemic in 2020, as a possible marker for changing epidemiology of head lice during the COVID pandemic. Data were collected from a large pharmacy chain in Israel, which provided the actual sales of pediculicides during the years 2010-2020. During the period 2010-2019 a significant increase of pediculicide sales from 281,986 - 498,107 was observed, the highest number being from 2019. In 2020, this number dropped to 294,477, a significant drop compared to previous years and to 2019. The results of this study suggest that head louse infestations are increasing in the last years, while the extended isolation of children due to COVID-19 influenced significantly the infestation rate of children with head lice.

Existence of immunological memory response in true sero-negative individuals post COVID-19 molecular diagnosis.

Approximately 1-8% of individuals do not develop antibodies following SARS-CoV-2 infection (sero-negatives). One BNT162b2 dose resulted in potent humoral response in 14 sero-negatives and 15 sero-positives, significantly higher than the response of 15 naïve-individuals, to two doses suggesting that COVID-19 provoked a memory response in individuals without detectable antibodies.

Rabies Vaccine Disposition: Trends in Vaccination Among Israeli Travelers.

Travelers are a risk-group for rabies; however, few are protected. We describe changes in pre-travel vaccination rates and post-travel referrals after animal contact. We conducted a nationwide, retrospective study for 2014-2018. The ratio of rabies vaccine courses distributed to travelers and the number of Israeli-tourist-entries to endemic countries was calculated, as was the proportion of travelers referred to a post-travel clinic after animal contact. During the study period, the ratio of pre-travel vaccine courses distributed nationally to outgoing tourism to endemic countries was stable at ≈0.7%; 13% of 256,969 pre-travel consultations included recommendation for rabies vaccination. Backpackers were more likely to be immunized (40.2%) than business travelers (4.4%) or travelers planning organized/high-end travel (2.0%). However, rates of rabies vaccination among backpackers showed a decline during the study period. Post-travel referrals after animal contact were stable at 2% of all referrals; most were exposed in Asia (69.5%) and 51% were bitten by dogs. Only 38% received post-exposure prophylaxis abroad. We conclude that only a minority of Israeli travelers, including backpackers, receive rabies pre-exposure prophylaxis. The proportion of travelers with potentially rabid animal contact is not decreasing; however, many exposed travelers do not receive post-exposure prophylaxis during travel. Because rabies control programs have been compromised in endemic countries during the COVID-19 pandemic, the need to provide rabies protection to travelers has become more urgent. After the ACIP's adoption of the World Health Organization's (WHO) 2-dose regimen, a revision of current vaccine guidelines is required to provide a simplified, more inclusive rabies vaccine policy.

The role of mouthwash sampling in SARS-CoV-2 diagnosis.

BACKGROUND: The current practice of COVID-19 diagnosis worldwide is the use of oro-nasopharyngeal (ONP) swabs. Our study aim was to explore mouthwash (MW) as an alternative diagnostic method, in light of the disadvantages of ONP swabs. METHODS: COVID-19 outpatients molecular-confirmed by ONP swab were repeatedly examined with ONP swab and MW with normal saline (0.9%). Other types of fluids were compared to normal saline. The Cq values obtained with each method were compared. RESULTS: Among 137 pairs of ONP swabs and MW samples, 84.6% (116/137) of ONP swabs were positive by at least one of the genes (N, E, R). However MW detected 70.8% (97/137) of samples as positive, which means 83.6% (97/116) out of positive ONP swabs, missing mainly Cq value > 30. In both methods, the N gene was the most sensitive one. Therefore, MW samples targeting N gene, which was positive in 95/137 (69.3%), are comparable to ONP swabs targeting E and R genes which gave equal results-95/137 (69.3%) and 90/137 (65.7%), respectively. Comparing saline MW to distilled water gave equal results, while commercial mouth-rinsing solutions were less sensitive. CONCLUSIONS: MW with normal saline, especially when tested by N gene, can effectively detect COVID-19 patients. Furthermore, this method was not inferior when compared to R and E genes of ONP swabs, which are common targets in many laboratories around the world.