Helmholtz Corona expertise

Basically, it is important to realize that there are infections with the novel coronavirus SARS-CoV-2 that proceed without symptoms. The disease caused by SARS-CoV-2 "Coronavirus Disease 2019" (COVID-19) can be quite different: From asymptomatic to very mild cases to severe pulmonary or even systemic diseases that can lead to multi-organ failure.

The virus initially replicates mainly in the nasal and pharyngeal cavities and occurs as early as 24 to 48 hours before symptoms appear. Especially in the initial phase of infection, the virus multiplies very rapidly. If infected persons exhale aerosols – tiny droplets that are released when speaking, singing, breathing, coughing or sneezing and remain in the air for hours – other persons who inhale these aerosols can become infected with the virus. As a result, the infection can also be transmitted by infected people who do not (yet) have any symptoms or who themselves have only very mild symptoms. Since these people often do not know that they are infected, they can easily become so-called "superspreaders".

In the first wave of infection in the spring of 2020, the virus was transmitted mainly by travelers returning from business trips or, for example, from skiing vacations. At that time, it was not yet known in detail how the virus spreads and to what extent, for example, protective mouth-nose masks also offer actual protection. As a result, it was mainly the elderly, for example in retirement and nursing homes, who became infected. During the course of the "second wave" after the summer of 2020, there were more young adults and children who became infected. These often have a milder case of the disease, but spread the virus within a short time due to an above-average number of social contacts, for example, in kindergarten or school. In the meantime, more older citizens are again becoming ill with COVID-19, which poses major challenges for hospitals and the healthcare system in general.

The dark figure quantifies the proportion of undetected COVID-19 cases. It is not a fixed figure. Rather, it varies in different regions, different age groups, and at different times during the pandemic. The number of unreported cases can only be estimated. It depends critically on existing testing strategies, testing capacities, and tracking capabilities. For this purpose, the blood of a section of the population, for example, is examined and it is determined what proportion has antibodies against the virus and these values are extrapolated to the total population.

Population-based seroprevalence studies and studies of antibody response in blood donors to date indicate a 2-6-fold underreporting of actual cases in adults following the first wave of the pandemic in Germany (1). The results show that, although a proportion of up to 16 percent of adults became infected with SARS-CoV-2 in some hotspots in the spring and early summer, seroprevalence was still much lower outside the hotspots. The underreporting factor ranged from 4 to 6.

In a study in which almost the entire locality was tested by PCR 6 weeks before study entry, the underreporting factor was only a factor of 2. In children, 6-fold  underreporting has been described (2). Thus, six times more children in Bavaria were infected with SARS-CoV-2 than reported. For the study, nearly 12,000 blood samples from children aged 1 to 12 years were examined between January and July 2020. Nearly half (47 percent) of the children with antibodies were asymptomatic.

This study highlights the discrepancy between reported infections and actual illness. Because many individuals, nearly half in children, do not develop symptoms typical of COVID-19, they are not tested. Therefore, population-based antibody screening is particularly important to more accurately determine the number of unreported cases and to better monitor the pandemic.

References:

1. Neuhauser H TR, Buttmann-Schweiger N,, Fiebig J OR, Poethko-Müller C, Prütz F,, Santos-Hövener C SG, Schaffrath Rosario A,, Wieler L SL. Results of seroepidemiological studies on SARS-CoV-2 in samples of the general population and blood donors in Germany (as of 12/3/2020). Epid Bull 2020;50.

2 Hippich M, Holthaus L, Assfalg R, Zapardiel Gonzalo JM, Kapfelsperger H, Heigermoser M, et al. Public health antibody screening indicates a six-fold higher SARS-CoV-2 exposure rate than reported cases in children. Med (N Y). 2020.

This depends heavily on how many cases and testing capacities Germany has overall. Representative testing is the key to a better understanding here. It is clear that reliable contact tracing is made more difficult with the current high number of new daily infections. To facilitate contact tracing, an information sharing app or similar mechanisms could be developed. If contact tracing has instrumental value (e.g., a direct reward as a thank-you), more people might be persuaded to do it. This is also shown by experience with morally relevant behaviors such as blood donation: Here, direct rewards usually work well.

Accurate, reliable virus detection methods enable successful containment of the SARS-CoV-2 pandemic. The gold standard is the detection of the RNA genome of SARS-CoV-2 in swabs from the nose and throat (respiratory examination materials) by RT-PCR testing.

Rapid antigen tests are less sensitive than the PCR tests. Although highly infectious individuals can be quickly identified if the swab is collected and the test is performed correctly. However, rapid antigen tests are somewhat less accurate.

The sensitivity of a test describes its ability to correctly identify individuals infected with SARS-CoV-2. As with PCR tests, the sensitivity of rapid SARS-CoV-2 antigen tests depends on several clinical factors: The viral load in the nasopharynx, the presence of symptoms, the timing of swab collection before or after symptoms appear, and, last but not least, the quality of a swab. Since these parameters can change very rapidly in the course of an infection and rapid antigen tests are only effective when the viral load is high, they represent only a snapshot. Therefore, the result is only meaningful for a limited period of about 24 hours. A negative test result does not exclude the risk of infecting others.

Particularly in a care situation or in close contact with relatives, a risk of infection may therefore remain even if the result of a rapid antigen test is negative. A negative test result is therefore not a "free pass" and does not release from strict adherence to hygiene measures and the protection of vulnerable groups of people in high-risk areas.

Rapid antigen tests are medical devices which, according to the Medical Devices Act, can be certified by the manufacturers themselves in the current exceptional situation and marked with a CE label. Here, sensitivities of 88.9 to 98.7 percent and specificities of 97.1 to 100 percent are reported by manufacturers for the approximately 200 SARS-CoV-2 antigen test systems listed to date. Specificity describes the ability to correctly identify those individuals who are not infected with SARS-CoV-2. However, initial investigations with SARS-CoV-2 antigen rapid tests from various manufacturers approved in Germany by independent, university diagnostic laboratories show in some cases a significantly lower performance.

For this reason, only those rapid antigen tests that meet the minimum criteria of the Paul Ehrlich Institute, the World Health Organization (WHO), and the European Centre for Disease Prevention and Control (ECDC) and have been tested in independent, published validation studies should be used to detect SARS-CoV-2. The minimum criteria are: The tests must have a sensitivity of at least 80 percent and a specificity of at least 97 percent.

Another requirement: To avoid misconduct and misinterpretation, SARS-CoV-2 antigen rapid tests should be performed only under the guidance of qualified personnel (usually laboratory personnel, hygienists or physicians, and trained nurses if necessary) in hospitalized patients, in residents of nursing homes and in outbreak situations. A positive test result must also be confirmed by a PCR test according to the specifications of the Robert Koch Institute (RKI).

Rapid antigen tests are suitable for various target groups and different scenarios. Possible applications include testing category 1 contacts after 5 days of quarantine, initial detection of outbreaks in nursing homes and homes for the elderly, testing patients with respiratory symptoms in doctors' offices, and shortening quarantine for school children to 7 days. Application in the context of discharge management or de-isolation of COVID-19 patients in interaction with the clinical-anamnestic criteria defined by the RKI is also conceivable.

Reference:

Position paper of the B-FAST network in the National Research Network of University Medicine on COVID-19 on the application and approval practice of rapid antigen tests for the detection of the new coronavirus SARS-CoV-2 (January 2021).

At the end of January, the first cases of the novel coronavirus SARS-CoV-2 were diagnosed in Germany. The initial clusters of confirmed cases were contained by intensive contact tracing and infection control measures. However, from March 2020 onward, momentum increased in Germany, and by mid-June 2020, slightly more than 190,000 laboratory-confirmed cases had been reported to the Robert Koch Institute (RKI). The RKI evaluated these cases in terms of disease severity in a retrospective, descriptive analysis.

With a share of 80 percent, the majority of infected persons had mild disease. At the same time, two thirds of the cases were younger than 60 years (the average age was 50 years). Severe cases were reported mainly for male infected persons aged 60 years and older with at least one risk factor (risk factors include in particular cardiovascular disease, diabetes, neurological disorders, and/or pulmonary disease). Sufferers aged 40 to 59 years had the longest time from onset of illness to hospital admission (median: six days). When admitted to an intensive care unit, they also had the longest period with treatment requiring intensive care (median: eleven days).

References:

RKI website: disease severity of the first COVID-19 wave in Germany based on notifications according to the Infection Protection Act - Journal of Health Monitoring S11/2020.

In the meantime, numerous valid studies document persistent complaints after COVID-19 disease, which can also occur after a mild case. These include, in particular, fatigue (state of persistent tiredness and exhaustion), memory and sleep disorders, headache, fever, cough, joint and muscle pain, shortness of breath or anxiety. A distinction is made between persistent organ damage (e.g., to the lungs, kidneys, and heart) due to the viral infection or inflammation, persistent sequelae due to complications of (intensive) therapy (e.g., lung remodeling after ventilation), and new-onset symptoms after the infection has subsided. Currently, post-COVID outpatient clinics are being established at several German hospitals, which can provide valuable information and counseling to patients. Overall, several years of observation are necessary to validly assess long-term sequelae. A good literature summary on possible long-term consequences can be found on the Center for Disease Control and Prevention (CDC) site.

Further information:

"Long-term effects of COVID-19: Permanently exhausted after infection?"

The current treatment regimens are summarized in guidelines. There is a guideline for inpatient treatment (S2k-Leitlinie - Empfehlungen zur stationären Therapie von Patienten mit COVID-19; AWMF-Register-Nr. 113/001; as of 23.11.2020) and for outpatient treatment (Neues Coronavirus SARS-CoV-2 - Informationen für die Hausärztliche Praxis; DEGAM S1- Handlungsempfehlung; AWMF-Register-Nr. 053-054).

Seven percent of COVID-19 patients require inpatient treatment. Most of these cases present with pulmonary dysfunction with reduced oxygen uptake and even respiratory failure. This is treated by controlled administration of oxygen until ventilation is achieved. Hospitalized patients also receive regular thromboprophylaxis with anticoagulant drugs such as low molecular weight heparin.

A reduction in mortality has only been shown for dexamethasone in high-quality trials (randomized, controlled). Therefore, this drug should be used in patients with severe COVID-19 disease. Other drugs have not yet been shown to be effective. Antiviral treatment with remdesivir, an agent approved in Europe, is used in the early phase of disease in some hospitalized patients. However, the use of Remdesivir is not recommended by the World Health Organization (WHO). The WHO also does not explicitly recommend other substances under investigation, e.g., chloroquine/hydroxychloroquine, azithromycin, interferon-beta-1b, or lopinavir/ritonavir. The same applies to the immunomodulatory drugs tocilizumab, anakinra, and blood plasma obtained from blood donors after successfully surviving the disease, the use of which is not recommended outside of clinical trials.

In the absence of effective outpatient treatment options for COVID-19 patients, it is particularly important to quickly identify those patients who are most likely to develop a severe course and require hospitalization. People over the age of 60 and men are at increased risk for severe disease progression. Other risk factors include cardiovascular disease, diabetes, and lung and kidney disease.

In addition to vaccination, another important component in fighting infections is the development of drugs against the pathogen. Currently, dozens of drug development studies against SARS-CoV-2 are underway worldwide and can be classified according to the type of substances being investigated.

The drugs under investigation are already approved drugs from the divisions of antiviral drugs, cardiovascular drugs, attenuating immunomodulators, drugs for pulmonary patients, and drugs of other types. The advantage here is that these approved substances no longer require time-consuming drug development processes such as studies on toxicity, bioavailability in the body or side effects. An example of this is the drug Remdesivir, which was originally developed and approved for the treatment of another virus, the Ebola virus. However, the World Health Organization (WHO) states that there is no clear evidence to date that Remdesivir noticeably improves the condition of COVID-19 patients. For this reason, WHO does not currently recommend the use of remdesivir.

In a growing number of projects, researchers are also trying to develop new drugs against SARS-CoV-2. Three classes of substances can be distinguished here:

1. Antibodies for passive immunization, which bind the virus and block its ability to infect cells.

2. Agents that specifically target viral factors that are necessary for viral replication (e.g., viral protease Mpro or viral RNA polymerase).

3. Drugs that target cellular factors that the virus needs for its replication (so-called host cell-directed therapy).

An overview of all ongoing projects for drugs and vaccines against COVID-19 can be found on the website of the US Milken Institute: https://docs.google.com/spreadsheets/d/16DbPhF9OD0MHHtCR12of6yUcfiRzP_-XGkynEbnipds/edit#gid=2075421071.

Helmholtz centers are also actively involved in the search for new drugs.

However, in addition to the search for new drugs, adequate targets in the multiplication cycle of SARS-CoV-2 need to be identified. This requires fundamental studies of the propagation strategy of the pathogen and its interaction with the cell. The goal is to find such targets (factors) whose inhibition efficiently prevents viral replication and at the same time does not or hardly affect the cell. This work is done at the Helmholtz centers in several ways. For example, the 3-D structures of viral proteins are deciphered and tested to determine how these proteins can be inhibited to block viral replication. Or cellular factors that play a key role in viral replication and spread (e.g. inhibitors of the receptor ACE2) are being sought. Finally, researchers are using high-resolution microscopy to study such changes in infected cells that may contribute to disease development. Active substances, on the other hand, should mitigate the severity of the disease.

Approximately 15 days after symptom onset, high levels of antibodies are found in the blood of infected individuals. Accordingly, the diagnostic quality of current antibody tests for the possible detection of infection is significantly increased at this time. For antibody tests measuring IgG and IgM antibodies, systematic reviews estimate sensitivity at 84 to 95 percent; specificity at 96 to 99.4 percent (1, 2). If IgG antibodies are detected, contact with SARS-CoV-2 can be assumed to have already occurred; positive IgM or IgA antibodies can possibly serve as indicators of recent contact. 

The sensitivity of a test describes its ability to correctly identify individuals infected with SARS-CoV-2. Specificity, on the other hand, describes the ability to correctly identify those individuals who are not infected with SARS-CoV-2. For the Euroimmune IgG S1 antibody test commonly used in Germany, sensitivities of 68 to 100 percent and specificities of 92 to 100 percent are found in diagnostic studies (3-42).

References:

1.         Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, et al. Antikörpertests zur Identifizierung einer aktuellen und zurückliegenden Infektion mit SARS-CoV-2. Cochrane Database of Systematic Reviews. 2020(6).

2.         Lisboa Bastos M, Tavaziva G, Abidi SK, Campbell JR, Haraoui LP, Johnston JC, et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ. 2020;370:m2516.

3.         Herroelen PH, Martens GA, De Smet D, Swaerts K, Decavele A-S. Humorale Immunantwort auf SARS-CoV-2. American Journal of Clinical Pathology. 2020;154(5):610-9.

4.         Manthei DM, Whalen JF, Schroeder LF, Sinay AM, Li S-H, Valdez R, et al. Differences in Performance Characteristics Among Four High-Throughput Assays for the Detection of Antibodies Against SARS-CoV-2 Using a Common Set of Patient Samples. Amerikanische Zeitschrift für klinische Pathologie. 2020.

5.         Zilla M, Wheeler BJ, Keetch C, Mitchell G, McBreen J, Wells A, et al. Variable Performance in 6 Commercial SARS-CoV-2 Antibody Assays May Affect Convalescent Plasma and Seroprevalence Screening. Amerikanische Zeitschrift für klinische Pathologie. 2020.

6.         Haselmann V, Kittel M, Gerhards C, Thiaucourt M, Eichner R, Costina V, et al. Comparison of test performance of commercial anti-SARS-CoV-2 immunoassays in serum and plasma samples. Clinica chimica acta; Internationale Zeitschrift für klinische Chemie. 2020;510:73-8.

7.         Manalac J, Yee J, Calayag K, Nguyen L, Patel PM, Zhou D, et al. Evaluation of Abbott anti-SARS-CoV-2 CMIA IgG and Euroimmun ELISA IgG/IgA assays in a clinical lab. Clinica chimica acta; Internationale Zeitschrift für klinische Chemie. 2020;510:687-90.

8.       Plebani M, Padoan A, Negrini D, Carpinteri B, Sciacovelli L. Diagnostische Leistungen und Schwellenwerte: Der Schlüssel zur Harmonisierung der serologischen SARS-CoV-2-Tests? Clinica chimica acta; Internationale Zeitschrift für klinische Chemie. 2020;509:1-7.

9.       Wolf J, Kaiser T, Pehnke S, Nickel O, Lübbert C, Kalbitz S, et al. Differences of SARS-CoV-2 serological test performance between hospitalized and outpatient COVID-19 cases. Clinica chimica acta; Internationale Zeitschrift für klinische Chemie. 2020.

10.       Wheeler SE, Shurin GV, Keetch C, Mitchell G, Kattel G, McBreen J, et al. Evaluation of SARS-CoV-2 prototype serologic test in hospitalized patients. Klinische Biochemie. 2020.

11.       Tang MS, Hock KG, Logsdon NM, Hayes JE, Gronowski AM, Anderson NW, et al. Clinical Performance of Two SARS-CoV-2 Serologic Assays. Klinische Chemie. 2020;66(8):1055-62.

12.       Hörber S, Soldo J, Relker L, Jürgens S, Guther J, Peter S, et al. Evaluation of three fully-automated SARS-CoV-2 antibody assays. Klinische Chemie und Labormedizin. 2020;58(12):2113-20.

13.       Tré-Hardy M, Wilmet A, Beukinga I, Dogné J-M, Douxfils J, Blairon L. Validation of a chemiluminescent assay for specific SARS-CoV-2 antibody. Klinische Chemie und Labormedizin. 2020;58(8):1357-64.

14.       Meyer B, Torriani G, Yerly S, Mazza L, Calame A, Arm-Vernez I, et al. Validation of a commercially available SARS-CoV-2 serological immunoassay. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2020;26(10):1386-94.

15.       Van Elslande J, Decru B, Jonckheere S, Van Wijngaerden E, Houben E, Vandecandelaere P, et al. Antibody response against SARS-CoV-2 spike protein and nucleoprotein evaluated by four automated immunoassays and three ELISAs. Klinische Mikrobiologie und Infektionen : die offizielle Veröffentlichung der Europäischen Gesellschaft für klinische Mikrobiologie und Infektionskrankheiten. 2020.

16.       Van Elslande J, Houben E, Depypere M, Brackenier A, Desmet S, André E, et al. Diagnostische Leistung von sieben IgG/IgM-Antikörper-Schnelltests und des Euroimmun IgA/IgG ELISA bei COVID-19-Patienten. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2020;26(8):1082-7.

17.       Velay A, Gallais F, Benotmane I, Wendling MJ, Danion F, Collange O, et al. Evaluation of the performance of SARS-CoV-2 serological tools and their positioning in COVID-19 diagnostic strategies. Diagnostische Mikrobiologie und Infektionskrankheiten. 2020;98(4):115181.

18.       Wolff F, Dahma H, Duterme C, Van den Wijngaert S, Vandenberg O, Cotton F, et al. Monitoring antibody response following SARS-CoV-2 infection: diagnostic efficiency of 4 automated immunoassays. Diagnostische Mikrobiologie und Infektionskrankheiten. 2020;98(3):115140.

19.       Jääskeläinen AJ, Kekäläinen E, Kallio-Kokko H, Mannonen L, Kortela E, Vapalahti O, et al. Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples. Euro surveillance : bulletin Europeen sur les maladies transmissibles = Europäisches Bulletin für übertragbare Krankheiten. 2020;25(18).

20.       Dörschug A, Schwanbeck J, Hahn A, Hillebrecht A, Blaschke S, Groß U, et al. Evaluation of the Xiamen AmonMed Biotechnology rapid diagnostic test COVID-19 IgM/IgG test kit (Colloidal gold). Europäische Zeitschrift für Mikrobiologie und Immunologie. 2020.

21.       Wellinghausen N, Voss M, Ivanova R, Deininger S. Evaluation of the SARS-CoV-2-IgG response in outpatients by five commercial immunoassays. GMS Infektionskrankheiten. 2020;8:Doc22.

22.       Rychert J, Couturier MR, Elgort M, Lozier BK, La'ulu S, Genzen JR, et al. Evaluation of Three SARS CoV-2 IgG Antibody Assays and Correlation with Neutralizing Antibodies. Die Zeitschrift für angewandte Labormedizin. 2020.

23.       Charlton CL, Kanji JN, Johal K, Bailey A, Plitt SS, MacDonald C, et al. Evaluation of Six Commercial Mid- to High-Volume Antibody and Six Point-of-Care Lateral Flow Assays for Detection of SARS-CoV-2 Antibodies. Zeitschrift für klinische Mikrobiologie. 2020;58(10).

24.       Patel EU, Bloch EM, Clarke W, Hsieh Y-H, Boon D, Eby Y, et al. Comparative performance of five commercially available serologic assays to detect antibodies to SARS-CoV-2 and identify individuals with high neutralizing titers. Zeitschrift für klinische Mikrobiologie. 2020.

25.       Theel ES, Harring J, Hilgart H, Granger D. Performance Characteristics of Four High-Throughput Immunoassays for Detection of IgG Antibodies against SARS-CoV-2. Journal of clinical microbiology. 2020;58(8).

26.       Beavis KG, Matushek SM, Abeleda APF, Bethel C, Hunt C, Gillen S, et al. Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;129:104468.

27.       Brochot E, Demey B, Handala L, François C, Duverlie G, Castelain S. Comparison of different serological assays for SARS-CoV-2 in real life. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;130:104569.

28.       Jääskeläinen AJ, Kuivanen S, Kekäläinen E, Ahava MJ, Loginov R, Kallio-Kokko H, et al. Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;129:104512.

29.       Kohmer N, Westhaus S, Rühl C, Ciesek S, Rabenau HF. Kurze klinische Bewertung von sechs Hochdurchsatz-SARS-CoV-2-IgG-Antikörper-Tests. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;129:104480.

30.       Marlet J, Petillon C, Ragot E, Abou El Fattah Y, Guillon A, Marchand Adam S, et al. Clinical performance of four immunoassays for antibodies to SARS-CoV-2, including a prospective analysis for the diagnosis of COVID-19 in a real-life routine care setting. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;132:104633.

31.       Montesinos I, Gruson D, Kabamba B, Dahma H, Van den Wijngaert S, Reza S, et al. Evaluation of two automated and three rapid lateral flow immunoassays for the detection of anti-SARS-CoV-2 antibodies. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;128:104413.

32.       Nicol T, Lefeuvre C, Serri O, Pivert A, Joubaud F, Dubée V, et al. Assessment of SARS-CoV-2 serological tests for the diagnosis of COVID-19 through the evaluation of three immunoassays: Zwei automatisierte Immunoassays (Euroimmun und Abbott) und ein schneller Lateral-Flow-Immunoassay (NG Biotech). Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;129:104511.

33.       Pflüger LS, Bannasch JH, Brehm TT, Pfefferle S, Hoffmann A, Nörz D, et al. Clinical evaluation of five different automated SARS-CoV-2 serology assays in a cohort of hospitalized COVID-19 patients. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;130:104549.

34.       Serrano MM, Rodríguez DN, Palop NT, Arenas RO, Córdoba MM, Mochón MDO, et al. Comparison of commercial lateral flow immunoassays and ELISA for SARS-CoV-2 antibody detection. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;129:104529.

35.       Weidner L, Gänsdorfer S, Unterweger S, Weseslindtner L, Drexler C, Farcet M, et al. Quantifizierung von SARS-CoV-2-Antikörpern mit acht kommerziell erhältlichen Immunoassays. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;129:104540.

36.       Wellinghausen N, Plonné D, Voss M, Ivanova R, Frodl R, Deininger S. SARS-CoV-2-IgG response is different in COVID-19 outpatients and asymptomatic contact persons. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2020;130:104542.

37.       Tuaillon E, Bolloré K, Pisoni A, Debiesse S, Renault C, Marie S, et al. Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients. The Journal of infection. 2020;81(2):e39-e45.

38.       Kohmer N, Westhaus S, Rühl C, Ciesek S, Rabenau HF. Klinische Leistungsfähigkeit verschiedener SARS-CoV-2-IgG-Antikörpertests. Zeitschrift für medizinische Virologie. 2020.

39.       Davidson N, Evans J, Giammichele D, Powell H, Hobson P, Teis B, et al. Vergleichende Analyse von drei laborgestützten serologischen Tests für SARS-CoV-2 in einer australischen Kohorte. Pathologie. 2020.

40.       Kowitdamrong E, Puthanakit T, Jantarabenjakul W, Prompetchara E, Suchartlikitwong P, Putcharoen O, et al. Antibody responses to SARS-CoV-2 in patients with different severities of coronavirus disease 2019. PloS one. 2020;15(10):e0240502.

41.       Naaber P, Hunt K, Pesukova J, Haljasmägi L, Rumm P, Peterson P, et al. Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Vergleich von neun Tests im Verhältnis zu klinischen Daten. PloS one. 2020;15(10):e0237548.

42.       Rikhtegaran Tehrani Z, Saadat S, Saleh E, Ouyang X, Constantine N, DeVico AL, et al. Performance of nucleocapsid and spike-based SARS-CoV-2 serologic assays. PloS one. 2020;15(11):e0237828.

This question still cannot be answered unequivocally. When infected with the SARS-CoV-2 coronavirus, the body produces antibodies that can fight the virus, as well as certain immune cells called T cells. The antibodies are usually detectable in the second week after the onset of the disease. However, among other things, the number of these antibodies decreases again over time, especially if the SARS-CoV-2 infection is without symptoms or the COVID-19 illness is accompanied by only mild symptoms. Re-infection (known as reinfection), although rare, is possible. High levels of virus have been detected in the nasal and pharyngeal passages of individuals who have been reinfected with SARS-CoV-2. This could mean that individuals who become repeatedly infected may also infect others. Accordingly, the AHA+L+A formula (distance, hygiene, everyday mask + ventilation + Corona warning app) should continue to be followed even after contracting COVID-19.

References:

1. https://www.infektionsschutz.de/coronavirus/fragen-und-antworten/krankheitsverlauf-und-immunitaet.html#faq4235
2. https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Steckbrief.html;jsessionid=8F33964FFEE5FC4ED2801DFD9CF91312.internet122?nn=13490888#doc13776792bodyText17

A vaccination prepares the body for a possible infection. And it does so in such a way that our immune system can fight off the pathogen and you don't get sick. A vaccine is usually injected for this purpose. It contains components or characteristics of the virus, but cannot trigger the disease.

But not all vaccines are the same. Sometimes only part of the virus is used, sometimes the complete virus but killed by heat, for example, sometimes a harmless viral variant that looks similar enough to the body. These "traditional" vaccines are also under development worldwide against coronavirus. But their production is often very lengthy. During the corona pandemic, vaccines based on new platform technologies were able to be adapted and developed most quickly to the new virus. These include the RNA vaccines from BioNTech/Pfizer and Moderna, respectively, or the adenovirus vaccine from Oxford University and AstraZeneca. The RNA vaccine from BioNTech/Pfizer has been used in Germany since late December, and the Moderna vaccine has been licensed in Europe since Jan. 6, 2021. Another RNA vaccine from CureVac is still undergoing clinical trials.

This marks the beginning of the major logistical challenge of large-scale application and equitable distribution of the vaccines. The Standing Commission on Vaccination (STIKO), with the participation of the Ethics Council and the German National Academy of Sciences Leopoldina, has drawn up recommendations for this. It is not yet possible to say how long the vaccines will provide protection, as no data are yet available on this. Follow-up studies will provide information on this.

The RNA vaccine consists of two parts: An RNA molecule and a lipid envelope. The RNA contains the building instructions for the small spikes of the corona virus, the spike protein, and the lipid envelope ensures that it enters human cells. Decades of research have succeeded in modifying the RNA so that the cell's protein factories translate the foreign RNA directly into the protein, just like the cell's own mRNA. Thus, the cell produces the spike protein of the virus and presents it on its surface. The immune system can now produce antibodies and other immune cells against the spikes. Once the correct virus enters the body after infection, it is recognized and fought by the antibodies.

For example, to test the effectiveness of the vaccines, in the case of BioNTech/Pfizer, about 18,000 people received the vaccine, and 18,000 people received only a shot of saline (control group). Over the course of several months, there were nearly 200 incidental infections in the control group, and only about a dozen in the vaccinated group. This uneven distribution shows that the vaccine is very effective. In addition, the researchers have demonstrated protection in animal studies with rhesus monkeys. Rhesus monkeys are naturally susceptible to infection with SARS-CoV-2 and also develop disease symptoms such as pneumonia. Thus, they are suitable animal models for COVID-19 disease. After administration of the experimental vaccine, the animals were exposed to the virus, but they were protected and infection was not detectable.

Reference:

https://www.mdc-berlin.de/de/news/news/so-wirken-die-impfstoffe-gegen-corona

In principle, it can be assumed that vaccination will significantly reduce the incidence of infection in the long term and represent one of the most important building blocks for long-term control of the virus. When and to what extent this will become apparent depends on the willingness of the population to be vaccinated, the availability of vaccines and the number of vaccinations per day. Based on current vaccination rates, a noticeable effect of vaccination on the incidence of infection is more likely in the second half of 2021. It must also be taken into account that precisely those groups that are vaccinated first for ethical reasons due to their particular risk - such as people over 80 years of age or residents of nursing homes – have the fewest social contacts and therefore also contribute the least to the overall incidence of infection. As a result, moderate effects can be expected for these first vaccinations in particular.

There are various model calculations for the incidence of infection. A study from the USA, for example, concludes that more than 75 percent of infections could be prevented by vaccination. This assumes vaccination of 1 percent of the population daily, 50 percent vaccination coverage overall, and a proportion of sterilizing immunity – meaning that vaccinated individuals also cannot transmit the virus – of 90 percent. Another model suggests that at a realistic vaccination rate for the United States of 40 percent of the population over 284 days, there could be a reduction in new infections to half after about 100 days compared with the expected trend without vaccination.

All of these models incorporate assumptions that are still subject to uncertainty. For example, it is not yet entirely clear in how many vaccinated individuals sterilizing immunity is generated, i.e., transmission is also prevented. Such assumptions can massively influence the model results. For basic considerations, one can assume that the reproduction number decreases proportionally to the share of the vaccinated in the total population and the share of sterilizing immunity among the vaccinated.

Containing the pandemic requires cooperation, consideration, and a willingness to be informed by as many people as possible. The following approaches can help support this:

a. Social norms and role models.

People respond to the behavior of others and follow social norms (see reviews in Bicchieri/Dimant 2019, Thaler/Sunstein 2008). The vast majority of the population wants to contain the pandemic. There is a (loud) minority that protests against measures. This must be taken seriously. But we must not forget to emphasize how great the support is among the population for many measures. Every individual can serve as an example. Even wearing a mouth-nose protection sends out a signal. The role model function of politicians, celebrities, etc. can also help.

b. Keep unavoidable risks as low as possible

People deal with probabilities differently than one would mathematically assume (Kahnemann/Tversky 1974). If there is already a clear unavoidable risk, e.g., due to children's school attendance, work, public transportation, doctor's visits, etc., additional risks (e.g., due to contacts during leisure time) are underestimated. In principle, unavoidable risks should be kept as small as possible. Doctors' offices, schools and public transport operators should do everything they can to feel as safe as possible. Other measures (e.g., doctor's appointments also on weekends or in the evenings, online consultation hours, using more buses and trains, equalized teaching, air scrubbers/filters, etc.) could help.

c. Make information experiential

Many people tend to ignore unpleasant information, both in the moral context and in the health context (Golman et al. 2017, Hertwig/Engel 2016, MacCoun et al. forthcoming). This is especially true when people do not want to acknowledge risks and/or maintain reckless behavior (Dana et al. 2007, Oster et al. 2013, Ganguly/Tasoff 2017, Szech/Schweizer 2018, Falk et al. 2020, Serra-Garcia/Szech 2019). This phenomenon of information avoidance can also be observed in dealing with the pandemic (Serra-Garcia/Szech 2020, Thunström et al. 2020a, b). However, people learn through experience and respond to informative nudges, so-called "nudges" (Malmendier/Nagel 2016, Thaler/Sunstein 2008). Visualizing risks (e.g., through CO2 traffic lights in stores, doctors' offices, schools, on trains, etc.), the mode of action of measures such as physical distancing, e.g., through simulations, good graphical presentation, and analogies (example: a virus cloud spreads like a puff of smoke) can therefore be very helpful.

d. Self-efficacy, practical tips, concrete outlook

People like to be active and see the results of their actions (Marshall 2009, Norton et al. 2012). This desire can go so far as to compromise moral values (Martensson-Pendrill 2006, Falk/Szech2020). How is it possible to motivate people to stay at home so that they still feel active and self-efficient and retain hope for better times? These measures can help:

Illustrate how much a few weeks of staying home can help in coping with the pandemic.
Make it clear that the time for tough measures will not be indefinite. Provide an outlook (tied to successes of the measures).
Give concrete examples of how to make time at home active and social: Calling friends and relatives so no one feels lonely. Children could paint or make crafts for grandparents. Grandparents can read over the phone (or Skype, etc.). Writing letters. Help shop for elderly neighbors, etc.
Idea competitions on how to enable social participation (e.g., digital platforms where people could help students with chores online, etc.).
Practical tips on how to keep yourself mentally and physically healthy (routines, self-care, exercise, etc.).

References:

1. Bicchieri, C., Dimant, E. Nudging with care: the risks and benefits of social information. Public Choice(2019). https://doi.org/10.1007/s11127-019-00684-6
2. Dana, Jason, Weber, Roberto A. and Jason Xi Kuang (2007). Exploiting Moral Wiggle Room: Experiments Demonstrating an Illusory Preference for Fairness. Economic Theory 33(1), 67-80.
3. Ganguly, Ananda R., and Joshua Tasoff (2017). Fantasy and Dread: The Demand for Information and the Consumption Utility of the Future. Man- agement Science 63 (12), 4037-4060.
4. Golman, Russell, Hagmann, David, and George Loewenstein (2017). Information Avoidance." Journal of Economic Literature 55 (1), 96-135.
5. Hertwig, Ralph and Christoph Engel (2016). Homo Ignorans Deliberately Choosing Not to Know." Perspectives on Psychological Science 11 (3), 359- 372.
6. MacCoun et al, forthcoming. Deliberate Ignorance: Choosing not to know, edited by R. Hertwig and C. Engel, MIT press.
7. Malmendier, U., Nagel, S. (2016). Learning from inflation experiences. The Quarterly Journal of Economics. 131(1): 53–87.
8. Marshall, A. (2009).Principles of economics: Unabridged eighth edition. Cosimo, Inc.
9. Martensson–Pendrill, A.-M. (2006). The manhattan project - a part of physics history.PhysicsEducation,41(6), 495–496.
10. Norton, M. I., Mochon, D., & Ariely, D. (2012). The ikea effect: When labor leads to love. Journal of Consumer Psychology 22, (3), 453–46
11. Oster, Emily, Shoulson, Ira, and E. Ray Dorsey (2013). Optimal Expectations and Limited Medical Testing: Evidence from Huntington Disease. American Economic Review 103 (2), 804-30.
12. Serra-Garcia, Marta and Szech, Nora, The (In)Elasticity of Moral Ignorance (August 1, 2019). CESifo Working Paper No. 7555, Available at SSRN: https://ssrn.com/abstract=3357132
13. Serra-Garcia, Marta and Nora Szech (2020). Demand for COVID-19 Antibody Testing, and Why It Should Be Free." CESifo Working Paper 8340.
14. Schweizer, N., Szech, N. (2018). Optimal Revelation of Life-Changing Information. Management Science 64(11) 4967-5460.
15. Thaler, R., & Sunstein, C. (2008). Nudge: Improving decisions about health, wealth, and happiness. New Haven: Yale University Press.
16. Thunström, L., Ashworth, M., Shogren, J., Newbold, S., Finnoff, D. (2020a). Testing for COVID-19: Willful ignorance or selfless behavior? Behavioural Public Policy, forthcoming.
17. Thunström, L., Ashworth, M., Finnoff, D., Newbold, S. (2020b, May 6). Hesitancy Towards a COVID-19 Vaccine and Prospects. Available at SSRN: https://ssrn.com/abstract=3593098
18. Tversky, A., Kahneman, D. (1974). Judgment under Uncertainty: Heuristics and Biases. Science 185(4157), 1124-1131.

Particular psychological distress from the pandemic is found among people with COVID-19, people with pre-existing mental disorders, and people who work in the health care system. Risk factors for being particularly affected in the general population also include: younger age (age range from 20 to late 40s), to a lesser extent female gender, relatives affected by COVID-19, feeling socially isolated, and feeling ill-informed. Further research is needed on these issues, as well as on the long-term effects on the psyche.

In acutely ill patients, the virus can affect the brain; acute states of confusion (delirium) are then frequently found. Symptoms of anxiety and depression are particularly prevalent in patients who require intensive care. People with pre-existing mental disorders may experience a worsening of their health. Physicians and nurses experience psychological stress especially when patients cannot be treated due to a lack of capacity. In the German general population, some (but not all) studies found an increase in perceived stress, depression and anxiety, and substance use (alcohol/cigarettes). Contrary to initial assumptions, young people were more affected than the older population.

There are different support options depending on the risk group. For acutely infected individuals, the focus is on treatment of the infection and measures to prevent delirium (e.g., stimulus shielding in the intensive care unit). People with pre-existing mental disorders should be treated in a disorder-specific and resource-oriented manner in order to actively utilize the patients' individual potential. Possibilities such as video consultation or digital applications can maintain contact with therapists even during isolation. In healthcare, so-called triage situations, in which doctors have to decide whom to treat first, must be avoided as far as possible. When this is not possible, decision-making processes should be designed to reduce the burden on those involved.

References:

• Vindegaard N, Benros ME. COVID-19 pandemic and mental health consequences: systematic review of the current evidence. Brain Behav Immun. 2020;89:531-542. 
• Kuehner C, Schultz K, Gass P, Meyer-Lindenberg A, Dressing H. [Mental health status in the community during the COVID-19 pandemic]. Psychiatric Practice. 2020. 
• Christian Goetzl M et al. Social isolation, mental health, and use of digital interventions in youth during the COVID-19 pandemic: a nationally representative survey.
• Heath C, Sommerfield A, von Ungern-Sternberg BS. Resilience strategies to manage psychological distress among healthcare workers during the COVID-19 pandemic: a narrative review. Anaesthesia. 2020;75:1364-1371

Isolation measures can lead to a mismatch between desired and actual social contacts, i.e., to loneliness and the feeling of social isolation. This is a chronic state of stress with negative consequences for mental health (anxiety disorders, depression) and also physical consequences, e.g., on the cardiovascular system. The likelihood of such ailments increases with the duration of isolation. Impending or actual loss of income is also a potential risk factor.

Appropriate prevention and intervention measures must therefore be part of pandemic crisis management. Findings from general stress research suggest that it helps to maintain familiar routines (e.g., in preparing for school or work), to emphasize areas of self-efficacy (decisions about daily structure, leisure activities), to be active on behalf of others (e.g., helping with shopping), and to obtain information about the pandemic situation in a measured and time-limited manner from sources one trusts. Special attention should be paid to self-care (healthy diet, adequate sleep at usual times, exercise).

It is helpful if those affected develop an attitude of acceptance toward the complexity of the situation. Negative feelings should be allowed, but positive feelings and aspects should also be emphasized (e.g., more time for family, no commuting). This attitude is helpful and can be fostered through evidence-based techniques. The level of evidence regarding interventions for loneliness is limited. However, in the pandemic situation, the channels for social interaction that are still possible should be used intensively, including through the use of audiovisual media. This includes meetings between two people as well as alternative formats for group activities, e.g., as videoconferencing.

References:

1. Rohr S, Muller F, Jung F, Apfelbacher C, Seidler A, Riedel-Heller SG. [Psychosocial Impact of Quarantine Measures During Serious Coronavirus Outbreaks: A Rapid Review]. Psychiatric Practice. 2020;47:179-189.
2. Galea S, Merchant RM, Lurie N. The Mental Health Consequences of COVID-19 and Physical Distancing: the Need for Prevention and Early Intervention. JAMA Intern Med. 2020;180:817-818. 
3. Masi CM, Chen HY, Hawkley LC, Cacioppo JT. A meta-analysis of interventions to reduce loneliness. Pers Soc Psychol Rev 2011;15:219-266.

Digital forms of communication as a whole are used much more during the pandemic than before. These include virtual meetings, online games, watching movies together in party mode, virtual dinner dates and the use of social media. This is offset by lockdowns and other measures to reduce social contact. Digital communication (e.g., keeping in touch by phone) is part of official recommendations for coping, e.g., by the World Health Organization (WHO) and national health services.

There is little scientific research on the effect of such technologies on subjective well-being and mental health. A pre-pandemic meta-analysis shows that phone calls and text messaging have a positive effect on personal well-being, whereas online games appear to have a negative effect (Liu et al., 2019). A negative correlation of video games and television, but not related to social media use, was also found with respect to academic performance (Adelantado-Renau et al. 2019).

With regard to the specific effects of COVID-19, there is little solid scientific evidence. A first study from Italy, which received feedback from 465 individuals, shows a tendency. According to this, the use of digital technologies is positively correlated with perceived social support. The greater this was, the less frequently feelings of loneliness, boredom, anger and irritability occurred. However, this perceived social support did not correlate with the degree of anxiety. Age and gender were influential factors studied (Gabbiadini et al., 2020). However, to get a more complete picture, these would need to be supplemented by many more factors and larger samples would need to be studied. It should also be considered that the use of digital forms of communication may be associated with barriers and that these means are not equally open to all.

References:

1. Adelantado-Renau, M., Moliner-Urdiales, D., Cavero-Redondo, I., Beltran-Valls, M. R., Martínez-Vizcaíno, V., & Álvarez-Bueno, C. (2019). Association between screen media use and academic performance among children and adolescents: a systematic review and meta-analysis. JAMA pediatrics, 173(11), 1058-1067.
2. Gabbiadini A, Baldissarri C, Durante F, Valtorta RR, De Rosa M, Gallucci M. Together Apart: the Mitigating Role of Digital Communication Technologies on Negative Affect During the COVID-19 Outbreak in Italy. Front Psychol. 2020 Oct 21;11:554678. doi: 10.3389/fpsyg.2020.554678. PMID: 33192807; PMCID: PMC7609360. 
3. Liu D, Baumeister RF, Yan C, Hu B. Digital communication media use and psychological well-being: a meta-analysis. Journal of Computer-Mediated Communication 2019, 24(5):259-273.

According to the latest knowledge, the transmission of SARS-CoV-2 between people in enclosed spaces occurs predominantly via tiny droplets suspended in the air, so-called bioaerosols. Bioaerosols are emitted in increasing numbers, in the order listed, during breathing, talking, singing, and shouting. Evaporation of the water content further reduces their size, allowing them to float in the air for a long time and thus disperse in the room [1]. Therefore, air exchange and filtration of air in closed rooms are effective measures to eliminate airborne germs such as SARS-CoV-2 [2].

Active ventilation through open windows, especially by means of drafts, is preferable, as this reduces germ counts as well as humidity and CO2 content of the air. However, active ventilation leads to high heat losses and increasing heating requirements, especially in winter. It should also be noted that when the temperature difference between the indoor and outdoor areas is small and there is no wind, there is little exchange. Displacement ventilation methods that feed fresh air into the lower part of the room and exhaust it in the ceiling area can more efficiently move aerosols out of the room. Here, the thermal effect caused by body heat is an advantage. It transports the aerosols to the ceiling, where they are extracted. The uniform distribution in the room is thus suppressed [3]. Displacement ventilation methods are particularly suitable for public transport. The proposal of the Max Planck Institute for Chemistry in Mainz [4] to help with pandemic containment, e.g., in schools, using a low-cost modular principle, also follows this concept of extraction above the heads of people in a room.

However, dynamic impulse input from moving people, heavy breathing, or loud talking without a mask cannot be accommodated locally with this approach. This is because the exhaled bioaerosols then spread horizontally through the breathing stream or are drawn into the wake of the moving person. Therefore, wearing a mouth-nose protection is recommended in this case. One measure to reduce the horizontal transport of bioaerosols at the head height of neighboring people is to erect Plexiglas shields, which provide some short-term separation of the breathing air of different people. However, this can only provide additional protection and cannot replace the wearing of masks.

Another technology option is the use of mobile or stationary room air purification systems [5], [6]. Stationary systems, so-called room air purification systems, are operated in some public buildings. In our latitudes, they are usually only provided if the air in rooms or buildings must meet high standards with regard to temperature, humidity, proportions of harmful gases or particle counts (e.g., in laboratories, workplaces, hospitals or museums) or if ventilation is not or only insufficiently possible (e.g., in large halls, malls or low-energy houses). Indoor air technology generally incurs high investment and operating costs.

Room air conditioning systems extract the stale air and supply fresh air from outside. In the case of mobile room air cleaners, on the other hand, an installed unit draws in air via a fan and returns it to the room through a particulate air filter. The filter consists of glass fiber mats, in which even smaller aerosol particles are effectively separated. Meanwhile, there are a number of mobile room air purification devices on the market, with which rooms can easily be retrofitted and the aerosol particle load can be halved in a few minutes by means of air exchange rates of > 6 per h [7]. At the moment, there is still a lack of comprehensive evaluation of such concepts and systems of recirculating air filtration with respect to SARS-CoV-2 and similar pathogens. Open questions exist, for example, in the arrangement of the devices and the airflow in the room. In addition, regular filter changes are necessary. The Indoor Air Hygiene Commission (IRK) at the Federal Environment Agency primarily recommends active ventilation. In the opinion of the IRK, the use of mobile air cleaners is only useful as a supplement if adequate ventilation is not possible [8].

When using mobile room air cleaners, further aspects must be considered. Continuous noise from the fans can impair well-being and the ability to concentrate. Another open question is the survivability of viruses in filters, especially at high humidity and continuous operation of the recirculating air units. Here, the state of knowledge regarding SARS-CoV-2 is still insufficient. Thermal and UV sterilization concepts are integrated in some commercial products. When using UV light, potential hazards of the radiation itself and of ozone formation must be taken into account. Improved concepts for killing viruses by means of selective heat input via microwaves are just as forward-looking here as filter materials functionalized with antiviral substances, such as those based on titanium oxide (TiO2). However, there is still a need for research and development in this area.

CO2 traffic lights can be useful in closed rooms to determine the air quality when there is a temporary exchange of air with the environment. They measure the amount of exhaled air, which is proportional to the amount of potential infectious aerosols. The integration of smart virus sensors with high detection quality in recirculating air systems would be an effective measure, as this would make it possible to detect the presence of infected persons. However, research in this area is still at a very early stage.

In summary, it can be said that stationary and mobile air purification systems can make a contribution to reducing the risk of infection with regard to the spread of virus-containing aerosols, but do not offer complete protection. In particular, for cases in which larger groups of people act dynamically (frequent changes of location, physical activity) and possibly also fall short of safety distances, even air purification can only reduce the risk of infection to a limited extent. Therefore, such technical measures are only effective in combination with the applicable hygiene and behavioral rules. They appear to make sense above all for old people's and nursing homes, offices, museums and concert halls with rather passive audiences. The effectiveness in busy environments (schools, shopping malls, sports halls and concert halls with highly active audiences) should be proven by further use-case specific investigations.

Since room air filtration can contribute to risk reduction, especially for vulnerable groups of people, at least the equipment of old people's and nursing homes with additional room air technology, be it stationary or mobile, should be considered. However, this in no way replaces the use of masks in case of close contact. In principle, it should be possible to quickly retrofit filters with appropriate deactivation of viruses in stationary systems or to use mobile systems as part of emergency measures. In the context of future developments, it should be borne in mind that the change in climate with significantly warmer summer periods, as well as the construction of low-energy houses, will inevitably lead to increased use of room ventilation technology. Here, measures for the demand-oriented operation of air filtration should be considered at an early stage for some classes of buildings, in particular old people's and nursing homes, schools, day-care centers, cultural facilities, restaurants, workplaces, etc.

References:

1. G. Buonanno, L. Stabile and L. Morawska, Estimation of airborne viral emission: Quanta emission rate of SARS-CoV-2for infection risk assessment, Environment International 141 (2020) 105794.
2. WHO 2020 Q&A: Ventilation and air conditioning in public spaces and buildings and COVID-19. https://www.who.int/news-room/q-a-detail/coronavirus-disease-covid-19-ventilation-and-air-conditioning-in-public-spaces-and-buildings
3. R.K. Bhagat, M. S. Davies Wykes, S. B. Dalziel and P. F. Linden: Effects of ventilation on the indoor spread of COVID-19, J. Fluid Mech. (2020), vol. 903, F1
4. https://www.mpic.de/4770837/eine-lueftungsanlage-fuer-schulen-zum-selberbauen
5. C. Kähler, T. Fuchs, R. Hain: Can mobile indoor air purifiers effectively reduce an indirect SARS-CoV-2 infection risk by aerosols? (08/05/2020) Universität der Bundeswehr München. https://www.unibw.de/lrt7/raumluftreiniger.pdf
6. J. Curtius, M. Granzin, J. Schrod: Testing mobile air purifiers in a school classroom: reducing the airborne transmission risk for SARS-CoV-2, University of Frankfurt, MedRxiv, https://doi.org/10.1101/2020.10.02.20205633
7. C. Kähler, T. Fuchs, R. Hain: Quantification of a Viromed Klinik Akut V 500 disinfection device to reduce the indirect risk of SARS-CoV-2 infection by aerosol particles, Universität der Bundeswehr München MedRxiv, doi.org/10.1101/2020.10.23.20218099
8. Use of mobile air purifiers as a ventilation-supporting measure in schools during the SARS-CoV-2 pandemic Statement by the Commission on Indoor Air Hygiene (IRK) at the Federal Environment Agency, November 16, 2020.
9. www.dlr.de/content/de/artikel/news/2020/04/20201103_dlr-testet-filtersystem-zur-verringerung-der-virenlast-in-raeumen.html

Severe cases of the disease are observed more frequently in the following groups of people, which is why they are assigned to the so-called risk groups:

• Elderly persons with a steadily increasing risk of a severe case from about 50-60 years of age. 85 percent of those who died of COVID-19 in Germany were 70 years old or older (median age: 82 years)
• Male gender (1, 2)
• Smokers (4, 5, 6) (weak evidence)
• Severely obese individuals
• Individuals with certain pre-existing conditions, without ranking (7, 8, 9):
  • Of the cardiovascular system (e.g., coronary artery disease and hypertension)
  • Chronic lung diseases (e.g. COPD)
  • Chronic kidney and liver diseases
  • Patients with diabetes mellitus (diabetes)
  • Patients with cancer
  • Patients with a weakened immune system (e.g., due to a disease associated with immunodeficiency or regular use of medications that can affect and lower immune defenses, such as cortisone)

References:

1. Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020.
2. Ortolan A, Lorenzin M, Felicetti M, Doria A, Ramonda R. Does gender influence clinical expression and disease outcomes in COVID-19? A systematic review and meta-analysis. International Journal of Infectious Diseases. 2020;99:496-504.
3. Link RKI: Disease severity of the first COVID-19 wave in Germany based on notifications according to the Infection Protection Act - Journal of Health Monitoring S11/2020).
4. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. New England Journal of Medicine. 2020;382(18):1708-20.
5. Vardavas CI, Nikitara K. COVID-19 and smoking: a systematic review of the evidence. Tobacco induced diseases. 2020;18:20.
6. Adams SH, Park MJ, Schaub JP, Brindis CD, Irwin CE, Jr. Medical Vulnerability of Young Adults to Severe COVID-19 Illness—Data From the National Health Interview Survey. Journal of Adolescent Health. 2020;67(3):362-8.
7. Karagiannidis C, Mostert C, Hentschker C, Voshaar T, Malzahn J, Schillinger G, et al. Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study. The Lancet Respiratory Medicine. 2020.
8. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. OpenSAFELY: factors associated with COVID-19 death in 17 million patients. Nature. 2020.
9. Nguyen LH, Drew DA, Graham MS, Joshi AD, Guo C-G, Ma W, et al. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. The Lancet Public Health.

During the propagation of the genetic information of SARS-CoV-2, errors occur that lead to a change in the genetic information, a so-called mutation. If a mutation is detrimental to the reproduction of the virus, this virus will not prevail against the non-mutated viruses and will therefore be displaced. However, if the mutation promotes the replication of the virus, the virus variant will prevail over the non-mutated viruses and become the dominant variant over time.

In the case of SARS-CoV-2, a number of such mutations have been described that appear to give the virus an advantage. The first of these variants occurred at the onset of the pandemic. It was a change at position 614 of the spike protein. This protein is responsible for the entry of SARS-CoV-2 into human cells by binding to the cellular receptor, ACE2. The variant with the mutation at position 614 was rare at the beginning of the pandemic but became dominant very quickly, suggesting that this mutation increases the transmissibility of the virus.

More recently, a number of other variants have been described, designated B.1.1.7, B.1.351, and P.1. Again, the mutations in these variants affect the spike protein, particularly the region around the receptor binding site. Most notable is the mutation at position 484 of the spike protein. This is found in the variants B.1.351 (occurrence in Germany in calendar week 6: 0.36 percent) and P.1 and is now regarded as a so-called "immune escape" mutation, since it enables the virus to partially escape the antibody response. It has arisen independently several times, both in South Africa and in Brazil. This fact underlines the biological importance for the adaptation of the virus to humans.

The mRNA vaccines on the market elicit a very strong immune response in those vaccinated, preventing symptomatic SARS-CoV-2 infections in about 95 percent of cases. Recent (preliminary) publications indicate that although vaccine efficacy against variant B.1.351 is diminished, it is still neutralized, so immune protection can be assumed based on current knowledge. AstraZeneca's vector vaccine, on the other hand, showed minimal protection against mild to moderate COVID-19 cases in infections with this variant in a recently prepublished study. However, no one had to be hospitalized or died from COVID-19 in this study, so it can be assumed that the vaccination protects against severe cases of disease and thus a clear clinical benefit of the vaccination can be seen here as well. The vaccine manufacturers are currently already working on adapted vaccines.

The most common variant in Germany is variant B.1.1.7 (occurrence in Germany in calendar week 6: 22 percent). The vaccines on the market combat this variant in a manner comparable to the original SARS-CoV-2. However, it has been shown that B.1.1.7 can spread more rapidly and has a higher reproductive number.

Using SARS-CoV-2 sequencing and targeted mutation detection, the spread of these variants is now being studied in Germany and the emergence of new variants is being monitored.

References:

1) 2nd report on viral variants of SARS-CoV-2 in Germany, in particular on Variant of Concern (VOC) B.1.1.7 (as of 17.02,2021).

2) Wu et al, 2021 bioRxiv 2021.01.25.427948; doi: https://doi.org/10.1101/2021.01.25.427948

3) Xie, X., Liu, Y., Liu, J. et al. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nat Med (2021). https://doi.org/10.1038/s41591-021-01270-4

4) WHO Interim recommendations for use of the AZD1222 (ChAdOx1-S [recombinant]) vaccine against COVID-19 developed by Oxford University and AstraZeneca (Feb 10, 2021).

5) 2nd report on virus variants of SARS-CoV-2 in Germany, in particular on Variant of Concern (VOC) B.1.1.7 (as of 17.02,2021).

6, 7, 8) Detailed daily updated information on mutations can be found on the homepage of the Robert Koch Institute, on the page "Coronavirus Variants and Mutations" of the New York Times and on the page "COVID Reference".

First, the Corona alert app could be expanded to include a feature that allows users to provide more data if they wish. Second, there should be more incentives for using the app that encourage others to use it. For example, the app could prompt users to enter phone numbers or frequent contacts, which could then be automatically shared with central authorities if (and only if) they test positive. In addition, the app could apply principles from behavioral science, including gamification, or provide up-to-date Corona news from the user's region (such as case maps, current local rules, medical news updates, practical ideas for individual protection and environment, practical tips on how to stay happy and healthy). Information about how many infected people there are in one's neighborhood compared to other neighborhoods nearby could lead to "friendly competition" in reducing COVID-19 cases.

In addition, the app could provide support for a more convenient (and privacy-friendly) version of current paper-based event contact tracking, e.g., through techniques such as CrowdNotifier (https://github.com/CrowdNotifier/documents). For example, if users can use the app and credibly signal this, they would no longer need to enter their contact information into lists of hairdressers, workplaces, bars, and restaurants, assuming they are open. For many people, using the app may feel safer and more efficient than current methods of contact tracking.

It would also be conceivable to offer two versions of the app: A more comprehensive one that uses more data and thus allows for more information, and a basic variant that uses less data. Anyone who voluntarily opts for the more comprehensive variant could find out more precisely where a risky contact took place, provided the other person also uses the more comprehensive version of the app. This could significantly increase the usefulness of the app's warnings. Currently, it is often difficult to assess from an app warning how close the contact really was and what risk might therefore exist. Currently, it would not be technically possible to identify the location where an infected person was encountered, but it is possible to identify corresponding time windows.

Further information:

Pandemic response: What does the Corona warning app do?