SARS-CoV-2 Research Articles

An Unusual Glomerulopathy with Subepithelial Deposits Having Microspherular Structures Following COVID-19 Vaccine

We report an unusual glomerulopathy with nephrotic syndrome and acute kidney injury almost two weeks after the second injection of SARS CoV-2 vaccine covishield, ChAdOx1-nCoV-19 in a 75-year-old healthy man. Kidney biopsy revealed segmental stage 1 membranous glomerulopathy and collapsing focal segmental glomerulosclerosis pattern with immune complexes on IF. Electron microscopy (EM) revealed aggregates of spherular microparticles along glomerular capillary walls. After starting him on steroids, his kidney functions gradually improved with significantly reduced proteinuria. Our patient seems to be the only reported SARS CoV-2 vaccine-induced early membranous nephropathy showing a collapsing focal segmental glomerulosclerosis pattern and immune complexes on IF with subepithelial deposits consisting of microspherular particles on EM.

Hospitalisations and humoral COVID-19 vaccine response in vaccinated rituximab-treated multiple sclerosis patients

BackgroundPatients with multiple sclerosis (MS) treated with anti-CD20 therapies such as rituximab may have increased risk of severe COVID-19 disease. Vaccination induces protective immunity, but humoral vaccine response is known to be attenuated in rituximab-treated MS-patients-patients, which has indicated a need for real world data on severe morbidity and mortality from COVID-19 after vaccination. MethodsRituximab-treated patients treated at Haukeland University Hospital were identified through the National MS Registry and invited to participate in the study by giving a consent and providing a blood sample 3 weeks or later after ordinary COVID-19- vaccination, i.e. 2 doses given with a standard interval of 3 weeks. Blood samples were analysed with Enzyme-Linked Immunosorbent assay (ELISA) to evaluate humoral vaccine response with screening test against receptor-binding domain (RBD) and confirmatory Spike IgG-specific ELISA. A haemagglutination test (HAT) was performed as a marker of neutralizing antibodies. Patient serum concentration of rituximab were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). Registry data from the Norwegian MS registry and information on hospitalization from patient records were collected and linked to laboratory results. Results111 patients were included in the study. A total of 7 (6.3%) were hospitalized due to COVID-19 disease during the observation period. No patient was admitted to ICU and there were no deaths. 34.2% did not have detectable titre of SARS CoV-2 Spike IgG antibodies, 72.1% did not have a detectable titre of SARS CoV-2 RBD antibodies, and 88.2% did not have a detectable HAT titre. There was a correlation between hospitalisation and the absence of SARS CoV-2 Spike IgG antibody titre, and between hospitalisation and MS disease duration, as well as between spike IgG antibody titre and CD19 B-cell count, time since last rituximab infusion, cumulative rituximab treatment time and total IgG level in the patients. ConclusionA substantial proportion of rituximab-treated MS-patients-patients did not have detectable humoral vaccine responses after 2 doses of COVID-19 vaccination. Despite this, the cumulative percentage of patients hospitalized with COVID-19 disease throughout the observation period of 22 months was low, and no patients required ICU treatment. The results support that vaccinated MS-patients treated with rituximab have a protective effect against serious Covid-19 infection.

External Quality Assessment Program for SARS-COV-2 Molecular Detection in Pakistan.

Amid coronavirus disease 2019 (COVID-19) pandemic, accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for diagnosis management and breaking down transmission chains. We designed a national external quality assessment panel (EQAP) for SARS-CoV-2 molecular detection comprising working laboratories nationwide. A molecular diagnostic EQA panel that consists of five samples for SARS CoV-2 testing was distributed to 141 public and private sector laboratories across country. These samples contain different concentrations of SARS-CoV-2 to evaluate the sensitivity of commercial kits available. Sensitivity among public and private sector laboratories was variable, particularly lower SARS-CoV-2 concentrations significantly increased the risk of false-negative tests, whereas Ct values of accurately tested SARS-CoV-2 specimens increased as concentration decreased. These findings highlighted that performance of used commercial kits was not significantly correlated to various extraction or PCR methods. This study highlights the need for a national external quality assessment panel (EQAP) in the country to improve the quality of the healthcare system while ensuring the accuracy and reliability of results. Furthermore, EQAPs can help laboratories meet accreditation and regulatory requirements. However, continued participation in EQAP is recommended for quality enhancement of laboratories.

Prevalence of non- SARS CoV-2 respiratory virus infection in children during COVID-19 pandemic in Chennai, South India.

Acute respiratory virus infections (ARIs) are a significant cause of morbidity and mortality among children worldwide. Respiratory viral infections in children have been significantly impacted during the COVID-19 pandemic. Variations in the prevalence of respiratory virus infections have been associated with the COVID-19 pandemic, which corresponds to the clinical epidemiology of community-acquired respiratory viruses. The aim of the present study was to investigate the prevalence of acute respiratory viral infection in COVID-19 negative children. The study included 100 SARS-CoV2 negative children with respiratory tract infections. Real-time polymerase chain reaction was used to determine the prevalence of respiratory viruses causing ARI in children. In our study, adenovirus and HRSV-A were predominantly reported in SARS-CoV2 negative children. The results of the study indicated that the incidence of viruses causing acute respiratory tract infections in children changed during the COVID-19 pandemic.

Hyaluronic acid fillers and SARS CoV-2 vaccination. Potential mechanisms associated with delayed inflammatory reactions

Hyaluronic acid fillers and SARS CoV-2 vaccination. Potential mechanisms associated with delayed inflammatory reactions

Expert System for Sars Cov-2 Disease with Comorbidities Using a Combination of Case Based Reasoning and Certainty Factor Methods

<p><em>Virus Sereve Acute Respirator Syndrome Corona Virus 2 (SARS COV-2) is a virus that is also caused by a corona virus which if exposed to this virus will cause a serious infection that has the potential to be life threatening. In various cases, it turns out that infection with the SARS COV-2 virus can have effects on several organs such as the lungs, heart, blood vessels, kidneys and liver. In this regard, some people think that the SARS COV-2 virus is a scary virus that makes people afraid to come to health services so that it has an impact on uncontrolled blood sugar and is prone to complications. To overcome the increase in mortality due to the SARS COV-2 virus with comorbidities with the help of artificial intelligence to build a knowledge-based system in the medical field for diagnosing SARS COV-2 with comorbidities using a combination of Case Based Reasoning and Certainty Factor methods. The Case Based Reasoning method is used as a rule to detect disease symptoms by diagnosing new cases based on old cases. While the Certainty Factor is used to increase the value of confidence and feasibility. The percentage of confidence value given by experts in order to get maximum results.</em></p>

Covid-19 Anosmia And Gustatory Symptoms As A Prognostic Factor

coronavirus pandemic has affected millions of people all across the globe. Along with fever sore throat respiratory difficulty anosmia and ageusia are important symptoms being seen. This study evaluates the prevalence of olfactory and gustatory dysfunction in patients with SARS CoV-2 infection and the severity and duration of altered taste and smell along with time taken for recovery. A total number of 300 patients that had tested positive for COVID 19 in lady hardinge medical college and associated hospitals were assessed for presence and severity of olfactory and gustatory dysfunction.

The development and implementation of a proficiency testing program for SARS-CoV-2 using dried tube specimens in resource-limited countries

IntroductionWhen COVID-19 hit the world in 2019, an enhanced focus on diagnostic testing for SARS-CoV-2 was essential for a successful pandemic response. Testing laboratories stretched their capabilities for the new coronavirus by adopting different test methods. The necessity of having external quality assurance (EQA) mechanisms was even more critical due to this rapid expansion. However, there was a lack of experience in providing the necessary SARS-CoV-2 EQA materials, especially in locations with constrained resources.ObjectiveWe aimed to create a PT (Proficiency testing) programme based on the Dried Tube Specimens (DTS) method that would be a practical option for molecular based SARS-CoV-2 EQA in Low- and Middle-Income Countries.MethodsBased on previous ISO/IEC 17043:2010 accreditation experiences and with assistance from the US Centers for Disease Control and Prevention, The Supranational Reference Laboratory of Uganda (adapted the DTS sample preparation method and completed a pilot EQA program between 2020 and 2021. Stability and panel validation testing was conducted on the designed materials before shipping to pilot participants in six African countries. Participants received a panel containing five SARS-CoV-2 DTS samples, transported at ambient conditions. Results submitted by participants were compared to validation results. Participants were graded as satisfactory (≥ 80%) or unsatisfactory (< 80%) and performance reports disseminated.ResultsOur SARS-CoV-2 stability experiments showed that SARS-CoV-2 RNA was stable (-15 to -25 °C, 4 to 8 °C, (18 to 28 °C) room temperature and 35 to 38 °C) as well as DTS panels (4 to 8 °C, 18 to 28 °C, 35 to 38 °C and 45 °C) for a period of 4 weeks. The SARS-CoV-2 DTS panels were successfully piloted in 35 test sites from Zambia, Malawi, Mozambique, Nigeria, and Seychelles. The pilot results of the participants showed good accuracy, with an average of 86% (30/35) concordance with the original SARS CoV-2 expectations.ConclusionThe SARS-CoV-2 DTS PT panel is reliable, stable at ambient temperature, simple to prepare and requires minimal resources.

Candida and Long Covid: Mannan Not from Heaven

The pandemic has supercharged growing awareness of the gut microbiome as a critical determinant of human health. “Long haulers” share microbiomes similar to those seen in myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia, all frequently associated with Candida overgrowth (CO). Candida can synthesize its own IDO, altering tryptophan metabolism (ATM). Zonulin, a circulating protein that increases intestinal and endothelial permeability, has emerged as a central player. Candida hyphal walls express proteins analogous to gliadin/gluten, e.g., celiac disease (CeD), and mannans, e.g., Crohn’s disease (CrD), that may trigger antigliadin and anti-Gq coupled GPCR auto-antibodies linked to their lectin binding domain respectively. Hyphal mannan may induce auto-antibodies to AT1Rs, α1-ARs, mAChRs, and β2-ARs, prominent in LC, and regulate T cell receptors (TCRs) and regulatory B cell function, compromised in not only LC (vitiligo, psoriasis, alopecia) but also SLE, RA, and many other autoimmune diseases. All are Gq coupled GPCRs. The spike protein S on SARS CoV2 can attach to both the ACE2 receptor (required for tryptophan absorption) and Toll-like receptor4 (TLR4) bearing endothelial cells and enterocytes. Spike protein S is persistent in most with LC and, as a ligand for TLR4, can also activate zonulin. S can also activate the NLRP3 inflammasome, as can candidalysin. This inflammasome is directly connected to dementia, cancer, autoimmunity and obesity. Candidalysin causes hypercitrullination, instrumental in creating ACPAs (anti-citrullinated peptide antibodies) linked to LC, MCAS (mast cell activation syndrome), HSD (hypermobility spectrum disorder), and APS (antiphospholipid syndrome). A hypothetical pathophysiologic model is proposed implicating pre-existing CO, aggravated by Covid-19, in not only the genesis of LC but also that of autoimmune disease, dementia, cancer, many chronic diseases, and aging.

Persistent hiccups after acute COVID-19 successfully treated with chlorpromazine: a case report

IntroductionHiccups are among the rare complications of COVID-19 infections. There are several published reports of persistent hiccups presenting during the acute COVID-19 period. However, there are very few published reports of persistent hiccups occurring in the post-acute COVID-19 period. Consequently, most clinicians may not be aware of this rare presentation. This case highlights an atypical presentation of persistent hiccups that manifested during the post-acute COVID -19 period that clinicians need to be aware of. The caseadds to the ever increasing body of knowledge about symptoms and signs associated with Severe Acute Respiratory Syndrome Corona Virus type 2 (SARS CoV-2) infection.Case presentationA 27 year old male black Zambian patient presented to the emergency department of our hospital with persistent hiccup, 35 days after the initial acute episode of COVID-19. This was associated with breathlessness. There were no other symptoms. He had no history of pulmonary, gastrointestinal, neurological disease or malignancy. He did not take any alcohol or smoke. He had never used any recreational drugs. He was employed as a monitoring and evaluation officer at one of the main COVID centres in the capital. On examination, the patient was anxious. Blood pressure was 141/82, pulse rate was 95 beats per minute, respiratory rate was 26 breaths per minute, temperature was 36.8C and oxygen saturation was 97% on room air. Systemic examination was normal. Chest X-ray and abdominal ultrasonography were normal. A rapid COVID-19 antigen test, and COVID-19 Polymerase Chain Reaction (PCR) test that were done the following day were negative. All other haematological and biochemical tests, including D-dimer and C-reactive protein (CRP), were also normal. A diagnosis of post-acute COVID-19 associated hiccups was made. The patient responded well to treatment with chlorpromazine 25 mg 8 hourly. The hiccups disappeared completely after the fourth dose of chlorpromazine.ConclusionThis is one of the few published cases of COVID-19 associated persistent hiccups, occurring more than a month after the initial presentation. Most of the published cases report hiccups occurring in the acute COVID-19 period. Consequently, hiccups occurring in the post-acute COVID-19 period may not be attributable to COVID-19. This case has highlighted the need to consider post-acute COVID-19 in the differential diagnosis of persistent hiccup.

Targeting NSP-13 protein of SARS CoV-2 with selected natural compounds: An in-silico approach

Targeting NSP-13 protein of SARS CoV-2 with selected natural compounds: An in-silico approach

Novel series of hydrazones carrying pyrazole and triazole moiety: Synthesis, structural elucidation, quantum computational studies and antiviral activity against SARS-Cov-2

The novel series of hydrazones carrying both pyrazole and triazole moiety were synthesized and characterized using single crystal X-ray diffraction studies. It is found that the compound crystallizes in the triclinic system in the space group P1̅. Hirshfeld analysis was carried out to visualize the noncovalent intermolecular interactions which are responsible for molecular packing in the crystal. Further, density functional theory (DFT) calculations were used to calculate optimized molecular structure, stability, and a few of the quantum chemical parameters. Derived results are in good agreement with the experimentally obtained results. Analysis of frontier molecular orbitals (HOMO and LUMO) and their energy gap of the optimized structure revealed that the compound is stable in the gaseous state. Molecular electron densities, and electrostatic potential maps provide the reactive site and charge distribution of triazole group. Quantum theory of atoms in molecules (QTAIM) and reduced density gradient (RDG) analysis were carried out to explore the weak interactions present in the molecule. In addition, the synthesized compound was investigated as an inhibitor for SARS CoV-2 protease using in-silico molecular docking analysis to understand the mode of binding. The docking results showed the good binding score with Mpro protease 6LU7. Further, molecular dynamics (MD) were carried out for the best hit docked complexes.

Production of functional antibodies from hyperimmune duck eggs for neutralization of new coronavirus SARS CoV-2

Production of functional antibodies from hyperimmune duck eggs for neutralization of new coronavirus SARS CoV-2

M Multi-Organ Histopathological Changes in SARS COV2 Infection: A Systematic Review and Meta-analysis

M Multi-Organ Histopathological Changes in SARS COV2 Infection: A Systematic Review and Meta-analysis

Diet Outcomes in Patients With COVID-19 Who Were Intubated and Proned

Objective: During the first wave of the COVID-19 (SARS CoV-2) pandemic, patients being treated for acute respiratory distress syndrome were proned while intubated with mechanical ventilation. In this study, we aimed to compare the diet outcomes at the time of acute hospital discharge of patients with COVID-19 who were proned while endotracheally intubated (ETT-proned) with those who were intubated with but not proned (ETT-supine). Design: The design used is a single-center, retrospective, descriptive study. Results: Between March 1, 2020, and August 2020, 193 critically ill adult patients with severe COVID-19 requiring endotracheal intubation with mechanical ventilation were referred for a swallowing evaluation at our acute care tertiary hospital; 114 of these patients were ETT-proned. At the time of discharge from the hospital, there was no significant difference in diet level between ETT-proned and ETT-supine patients. Significant factors associated with restricted diet at discharge included older age ( p &lt; .001) and non–English-speaking status ( p = .05). Conclusions: In this study, diet levels at the time of discharge did not differ significantly between the patient groups by time of discharge. These results should be interpreted with caution in relation to the clinical swallow evaluation, which was curtailed by practice restrictions imposed by pandemic protocols. Future research should objectively assess swallow function in patients who were proned during intubation with mechanical ventilation, utilizing evidence-based swallow screening protocols, standardized assessment of physiology via imaging (videofluoroscopic swallow studies or flexible endoscopic evaluation of swallowing), and long-term follow-up to directly and objectively determine the impact proning has on swallow physiology.

Brief overview of mpox: To worry or to ignore?

Mpox was first discovered in the Democratic Republic of Congo as a zoonotic infectious disease with various possible transmission routes. Currently, it is a reemerging disease being monitored by the World Health Organization (WHO) after a surge of reported cases in several non-endemic countries in May 2022 and August 2023. This study probes into the issue of whether mpox should or should not be concerned as a potential threat during and after the current COVID-19 pandemic. Literature reviews were conducted using PubMed, DOAJ, and Cochrane to understand and synthesize more information on the virulence and lethality of mpox. The keywords used included “monkeypox”, “outbreak”, “reemerging infectious disease”, “southeast asia”, “smallpox”, “sars cov”, and “transmission”, which were all associated with the Boolean operators “AND” and “OR”. A total of 30 articles acquired from various journals and international official websites were included in this study. The sudden outbreaks across the Asia-Pacific region may be attributed to countries lifting their travel restrictions. Studies have shown that mpox has similar transmission routes to COVID-19 and manifests similar symptoms to smallpox. However, mpox needs prolonged contact for its transmission and has a lower case fatality rate (CFR). Several studies highlighted that current outbreaks have different epidemiological and clinical characteristics from classic cases. Mpox is not as highly transmissible as COVID-19 and not as severe as smallpox, but it still poses a potential threat to human health and needs further observation and immediate containment to prevent further transmission worldwide. The preparation of smallpox vaccination in case of emergency and further clinical trials of smallpox drugs are recommended.

Rapid Determination of SARS-CoV-2 Integrity and Infectivity by Using Propidium Monoazide Coupled with Digital Droplet PCR.

SARS-CoV-2 is a highly infectious virus responsible for the COVID-19 pandemic. Therefore, it is important to assess the risk of SARS-CoV-2 infection, especially in persistently positive patients. Rapid discrimination between infectious and non-infectious viruses aids in determining whether prevention, control, and treatment measures are necessary. For this purpose, a method was developed and utilized involving a pre-treatment with 50 µM of propidium monoazide (PMAxx, a DNA intercalant) combined with a digital droplet PCR (ddPCR). The ddPCR method was performed on 40 nasopharyngeal swabs (NPSs) both before and after treatment with PMAxx, revealing a reduction in the viral load at a mean of 0.9 Log copies/mL (SD ± 0.6 Log copies/mL). Furthermore, six samples were stratified based on the Ct values of SARS-CoV-2 RNA (Ct < 20, 20 < Ct < 30, Ct > 30) and analyzed to compare the results obtained via a ddPCR with viral isolation and a negative-chain PCR. Of the five samples found positive via a ddPCR after the PMAxx treatment, two of the samples showed the highest post-treatment SARS-CoV-2 loads. The virus was isolated in vitro from both samples and the negative strand chains were detected. In three NPS samples, SARS CoV-2 was present post-treatment at a low level; it was not isolated in vitro, and, when detected, the strand was negative. Our results indicate that the established method is useful for determining whether the SARS-CoV-2 within positive NPS samples is intact and capable of causing infection.

Structural, dynamic behaviour, in-vitro and computational investigations of Schiff’s bases of 1,3-diphenyl urea derivatives against SARS-CoV-2 spike protein

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from − 4.73 to − 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.

Evaluating the efficiency of ELISA, monoplex and multiplex probe-based real-time reverse-transcription PCR assays in the detection of SARS-CoV-2 (COVID-19) and influenza A and B viruses: A cross-sectional study.

The current study aimed to evaluate the efficiency of Enzyme-linked immunosorbent assay (ELISA) assay and monoplex and multiplex real-time reverse-transcription PCR (rRT-PCR) in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A and B viruses (Flu A and Flu B). The SARS-CoV-2 -specific IgG and IgM antibodies, as well as, Flu A (H1N1 and H3N2 serotypes) and Flu B virus antibodies were determined by ELISA assay. The one-step qRT-PCR method was used to detect the SARS-CoV-2 in nasopharyngeal swab samples. Furthermore, the presence of Flu A and B viruses was evaluated using probe-based RT-PCR. Simultaneous detection of SARS-CoV-2, Flu A and B viruses was performed by multiplex rRT-PCR assay. SARS CoV-2 IgM and IgG antibodies were detected in 33.3% and 58.3% of patients, respectively. In contrast, the SARS CoV-2 genome was detected in 50% of patients using the one-step monoplex RT-PCR assay. Flu A serotypes H1N1 and H3N2 were found in 16.7% and 8.3% of patients. Probe-based RT-PCR revealed that 39.3% of patients were positive for the Flu A virus. Multiplex rRT-PCR detect the SARS-CoV-2, Flu A, and Flu B in 50%, 39.3%, and 19% of samples, respectively. The sensitivity and specificity of multiplex rRT-PCR assay in comparison to monoplex RT-PCR were 100% and 55%, respectively. Coinfection with SARS-CoV-2, Flu A, and Flu B viruses was found in 9.5% of patients. Multiplex rRT-PCR can be used as a repaid, cost-effective and suitable tool for molecular surveillance of SARS-CoV-2 and Flu A/B viruses.

Vaccination against COVID-19 among healthcare workers as a cocoon strategy for people living with HIV

IntroductionHealthcare professionals working in infectious disease units are often engaged in the care of patients with HIV infection. A cocoon vaccination strategy may protect those who are immunocompromised from a severe course of COVID-19. MethodsThe research was conducted between January 2021 and June 2022. The study participants were 450 healthcare workers (HCWs) from the Hospital for Infectious Diseases in Warsaw who were vaccinated against COVID-19 with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) –, thefirst available type of vaccine in Poland. Sera were collected according to the schedule of the study. Statistical analyses were performed with non-parametric tests: Wilcoxon's test was used to compare dependent numerical variables, and Fisher's exact test and the Chi-squared test to compare categorical variables. A p value of <0.05 was considered statistically significant. ResultsAmong the 450 HCWs working in the Hospital for Infectious Diseases in Warsaw 412 (91,5 %) were vaccinated against COVID-19. In total 170 (41,3 %) vaccinated HCWs were included in the final analysis. Their median age was 51 years [interquartile range (IQR): 41–60 years] and median body mass index (BMI) was 25.10 [IQR: 22.68–29.03]. Most of the cohort consisted of women (n = 137, 80.59 %), with the majority working directly with patients (n = 137, 73.21 %). It was found that as early as 14 days after the second dose of the vaccine, 100 % of the study participants achieved a positive result for SARS CoV-2 S-RBD antibodies. There were 168 subjects who had had a COVID-19 diagnosis before entering study and after vaccination 65 HCWs was diagnosed with COVID-19. ConclusionsDue to the fact that people living with HIV with severe immunodeficiency may have an incomplete immune response to COVID vaccination and be at risk of a severe course of the disease, the cocoon strategy of vaccinating medical personnel may be beneficial for these patients.