There are many ways you can tell if a computer is safe, but it takes multiple layers of protection. It would be unwise to say that just because your computer is running antivirus, that you 100% free of threats. A computer should be protected not just from Malware, but physical threats as well. It is important to lock down a computer and if a PC is used in public spaces, to ensure the computer is protected by observing for strange behavior or if a PC has been tampered with. Modern Computers use bit locker to encrypt data and modern 2.0 TPM devices for cryptic operations
Beyond this however there is the layer of protection that is often overlooked, but the most important of all. People themselves. Practicing good computer hygiene is the best was to protect your device from attack. It is important to clean up old programs and only install programs from trusted sources. Programs that are not verified as safe from a trusted provide could potentially contain malware that could adversely affect your system. Some of which you may not know are installed until after the program has already harvested important information such as passwords and account username. Phishing, whaling, smishing and other forms of malicious emails are also one of the biggest threats facing a computer system. Inspecting E-mails and identifying clues such as urgency and the content of an E-mail can help you from making costly mistakes. In general, scams asking for money or payments, especially those with a sense of urgency should always be approached cautiously. Steps like identifying headers and verifying content with the supposed sender are steps worth taking to avoid a breach of your system or accounts. Taking steps such as 2FA will also protect your accounts and computers from unauthorized access. Also, be sure to not rely heavily on passwords as these can be easily guessed or cracked, especially if they lack a specific amount of complexity.
Enterprise systems specifically use multiple approaches of the combined methods above to ensure integrity of computers with a network such as 2FA, employee training and antivirus software.